<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03281954</url>
  </required_header>
  <id_info>
    <org_study_id>NSABP B-59/GBG 96-GeparDouze</org_study_id>
    <secondary_id>2017-002771-25</secondary_id>
    <secondary_id>MO39875</secondary_id>
    <nct_id>NCT03281954</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Neoadjuvant Chemotherapy With Atezolizumab or Placebo in Patients With Triple-Negative Breast Cancer Followed After Surgery by Atezolizumab or Placebo</brief_title>
  <official_title>A Randomized, Double-Blind, Phase III Clinical Trial of Neoadjuvant Chemotherapy With Atezolizumab or Placebo in Patients With Triple-Negative Breast Cancer Followed by Adjuvant Continuation of Atezolizumab or Placebo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>NSABP Foundation Inc</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>NSABP Foundation Inc</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to learn if the usual chemotherapy given before surgery&#xD;
      (neoadjuvant therapy) for breast cancer plus the experimental drug, atezolizumab, is better&#xD;
      than the usual chemotherapy plus a placebo. (A placebo is a drug that looks like the study&#xD;
      drug but contains no medication.) The usual chemotherapy in this study is paclitaxel (WP) and&#xD;
      carboplatin followed by doxorubicin and cyclophosphamide (AC) or epirubicin and&#xD;
      cyclophosphamide (EC). Usually, after neoadjuvant therapy and surgery for triple negative&#xD;
      breast cancer, no additional treatment is given unless the cancer returns. This study will&#xD;
      also look at continuing treatment after surgery with atezolizumab or the placebo. To be&#xD;
      better, atezolizumab given with the neoadjuvant therapy should be better at: 1) decreasing&#xD;
      the amount of tumor in the breast than the placebo given with the usual chemotherapy and 2)&#xD;
      decreasing the chance of the cancer from returning after surgery.&#xD;
&#xD;
      Another purpose of this study is to test the good and bad effects of atezolizumab when added&#xD;
      to the usual chemotherapy. Atezolizumab may keep your cancer from growing but it can also&#xD;
      cause side effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      NSABP B-59/GBG 96-GeparDouze is a prospective, randomized, double-blind, Phase III clinical&#xD;
      trial. This is a collaborative study being conducted by NSABP Foundation, Inc. in partnership&#xD;
      with the German Breast Group (GBG), and supported by funding by Genentech, a Member of the&#xD;
      Roche Group, and F. Hoffmann-La Roche, Ltd.&#xD;
&#xD;
      In this clinical trial of neoadjuvant and adjuvant administration of atezolizumab/placebo in&#xD;
      patients with high risk triple-negative breast cancer, the potential incremental efficacy and&#xD;
      safety of neoadjuvant administration of atezolizumab/placebo with a sequential regimen of&#xD;
      weekly paclitaxel with every-3-week carboplatin followed immediately by neoadjuvant&#xD;
      administration of atezolizumab/placebo with AC/EC will be evaluated. Patients will then&#xD;
      undergo surgery. Following recovery from surgery, patients will initiate approximately 6&#xD;
      months of adjuvant therapy with atezolizumab/placebo and receive the same investigational&#xD;
      agent they received pre-operatively. Administration of radiation therapy will be based on&#xD;
      local standards at the discretion of patients and investigators, but if administered,&#xD;
      atezolizumab/placebo will be administered concurrently. Adjuvant atezolizumab/placebo may be&#xD;
      delayed until after completion of radiation therapy per investigator discretion. Patients&#xD;
      with residual invasive cancer at the time of surgery may receive capecitabine concurrently&#xD;
      with atezolizumab/placebo in the adjuvant setting per investigator discretion and local&#xD;
      guidelines. Patients with germline BRCA1 or BRCA2 mutations with residual invasive cancer at&#xD;
      the time of surgery may receive olaparib in the adjuvant setting per investigator discretion&#xD;
      and local guidelines. Patients receiving olaparib must discontinue atezolizumab/placebo.&#xD;
&#xD;
      The primary aims of the study are 1) to determine value of atezolizumab in improving&#xD;
      pathologic complete response in the breast and post-therapy lymph nodes evaluated&#xD;
      histologically (pCR breast and nodes [(ypT0/Tis ypN0)]), and 2) to determine the value of&#xD;
      atezolizumab in improving event-free survival (EFS). Secondary aims include: pathologic&#xD;
      complete response in the breast (ypT0/Tis); pathologic complete response in the breast and&#xD;
      lymph nodes (ypT0 ypN0); positive nodal status conversion rate; overall survival;&#xD;
      recurrence-free interval: distant disease-free survival; brain metastases free survival; and&#xD;
      toxicity. The stratification factors for the study are: 1) clinical size of the primary tumor&#xD;
      (1.1-3.0 cm; &gt; 3.0 cm); 2) nodal status as determined by protocol-specified criteria&#xD;
      (negative, positive); 3) AC/EC (every 2 weeks; every 3 weeks); and 4) Region (North America;&#xD;
      Europe).&#xD;
&#xD;
      For patient eligibility, local testing on the diagnostic core must have determined the&#xD;
      patient's tumor to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP&#xD;
      guidelines. Material from either the diagnostic core biopsy or the research biopsy must be&#xD;
      sent for central testing for confirmation of ER, PgR, and HER2 to confirm eligibility. If&#xD;
      local testing has determined a tumor to be HER2 equivocal or to have a borderline ER/PgR&#xD;
      status (% IHC staining &lt; 10% for both), material may be submitted for central testing to&#xD;
      determine eligibility.&#xD;
&#xD;
      In order to proactively identify and further assess any cardiac toxicity that may occur with&#xD;
      the combination of anthracyclines and atezolizumab, this study includes a cardiac safety&#xD;
      lead-in for the first 60 patients who initiate AC/EC. The safety lead-in will consist of&#xD;
      assessment of ECG and serum troponin-T obtained just prior to administration of the first&#xD;
      dose of AC/EC, following completion of the administration of the 1st and 3rd cycle of AC/EC&#xD;
      prior to initiation of the atezolizumab/placebo. An additional assessment of LVEF with&#xD;
      echocardiogram or MUGA scan will also be obtained prior to the 3rd dose of AC/EC. In order to&#xD;
      provide an early assessment of cardiac safety, results of the troponin-T assessments, ECGs,&#xD;
      LVEF assessment, and cardiac safety data will be evaluated by the Data Safety Monitoring&#xD;
      Board (DSMB) when the last of the initial 20 patients who initiate AC/EC undergo their&#xD;
      scheduled post-surgery LVEF assessment. When the last of the first 60 patients to initiate&#xD;
      AC/EC undergo their scheduled post-surgery LVEF assessment, results of the troponin&#xD;
      assessments, ECGs, LVEF assessments, and cardiac safety data from all 60 patients will be&#xD;
      evaluated by the DSMB.&#xD;
&#xD;
      Research core biopsies of breast primary at baseline and 1-4 days prior to the second dose of&#xD;
      atezolizumab/placebo are a study requirement for all patients. One to three representative&#xD;
      blocks of residual primary tumor containing the maximum amount of tumor and node with the&#xD;
      largest focus of metastasis is required from the definitive breast surgery if gross residual&#xD;
      disease is greater than or equal to 1.0 cm. If gross residual disease is less than 1.0 cm,&#xD;
      tissue should be submitted, if possible. Blood specimens will be collected on all patients at&#xD;
      baseline for exploratory biomarker analysis and to support future correlative studies.&#xD;
&#xD;
      Accrual to NSABP B-59/GBG 96-GeparDouze began in December 2017 and was completed in May 2021&#xD;
      with a total of 1550 patients randomized. Based on actual accrual and the decision to&#xD;
      eliminate pCR as a co-primary endpoint, we recalculated the power to detect a hazard ratio of&#xD;
      0.70 attributed to the addition of atezolizumab, assuming a lost-to-follow-up rate of 0.00083&#xD;
      per month, using the actual accrual pattern for the power calculation. With 1550 patients&#xD;
      accrued in 42 months, an additional 22 months follow up will allow us to obtain 252 events&#xD;
      under the assumptions stated above, which will provide 80% power to detect a HR of 0.7&#xD;
      between the atezolizumab and the placebo arm at an overall 2-sided alpha level of 0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 19, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Event-free survival (EFS)</measure>
    <time_frame>From randomization until event, through study follow up to the time target number of events is obtained, up to 5 years</time_frame>
    <description>Time from randomization until event</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From date of randomization through study follow-up, to the time the target number of events is obtained, up to 5 years</time_frame>
    <description>Time from randomization until death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0)</measure>
    <time_frame>Following completion of neoadjuvant therapy (ypT0/Tis ypN0)</time_frame>
    <description>Absence of any invasive component in the resected breast specimen and all resected lymph nodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distant disease-free survival (DDFS)</measure>
    <time_frame>From date of randomization through study follow-up, to the time the target number of events is obtained, up to 5 years</time_frame>
    <description>Time from randomization until distant recurrence, death from breast cancer, death from other causes, and second primary invasive cancer (non-breast)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-free survival (DFS)</measure>
    <time_frame>From the first breast surgical procedure to the first disease recurrence or death from any cause</time_frame>
    <description>Ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, ipsilateral or contralateral DCIS, second primary non-breast invasive cancer and death attributable to any cause including breast cancer, non-breast cancer, or unknown cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of Adverse Events</measure>
    <time_frame>From beginning of study therapy to 90 days after last dose of study therapy</time_frame>
    <description>Frequency of adverse events graded according to the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of immune Adverse Events of Special Interest</measure>
    <time_frame>From beginning of study therapy to 90 days after last dose of study therapy</time_frame>
    <description>Frequency of immune adverse events of special interest according to the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac safety lead-in (Troponin-T)</measure>
    <time_frame>prior to initial dose of AC/EC following completion of carboplatin/paclitaxel co-administered with atezolizumab/placebo, approximately 12 weeks</time_frame>
    <description>Troponin-T levels in blood prior to initial dose of AC/EC following completion of carboplatin/paclitaxel co-administered with atezolizumab/placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac safety lead-in (Troponin-T)</measure>
    <time_frame>After administration of the 1st dose of AC/EC prior to administration of atezolizumab/placebo, approximately 1 hour after beginning the 1st dose of AC/EC</time_frame>
    <description>Troponin-T levels in blood after administration of the 1st cycle of AC/EC prior to administration of atezolizumab/placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac safety lead-in (Troponin-T)</measure>
    <time_frame>After administration of the 3rd dose (Cycle 3; each cycle is 21 days) of AC/EC prior to administration of atezolizumab/placebo, approximately 1 hour after beginning the 3rd dose of AC/EC</time_frame>
    <description>Troponin-T levels in blood after administration of the 3rd cycle of AC/EC prior to administration of atezolizumab/placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)</measure>
    <time_frame>Prior to initiation of carboplatin/paclitaxel and atezolizumab/placebo, at baseline</time_frame>
    <description>LVEF levels measured at baseline prior to initiation of carboplatin/paclitaxel and atezolizumab/placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)</measure>
    <time_frame>Prior to the 3rd cycle (each cycle is every 21 days) of AC/EC, approximately 6 weeks after initiation of AC/EC</time_frame>
    <description>LVEF levels measured before 3rd cycle of AC/EC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)</measure>
    <time_frame>Four to 6 weeks after surgery</time_frame>
    <description>LVEF levels measured after surgery</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1550</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>IV infusion once every 3 weeks for 4 doses (Cycle 1), once every 3 weeks for 4 doses (Cycle 2) and once every 3 weeks after surgery for 1 year after first dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atezolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IV infusion, 1200mg, once every 3 weeks for 4 doses (Cycle 1), once every 3 weeks for 4 doses (Cycle 2) and once every 3 weeks after surgery for 1 year after first dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Following randomization, patients will receive Paclitaxel 80 mg/m2 IV weekly x 12 doses + Carboplatin AUC of 5 IV Day 1 every 3 weeks for 4 cycles + placebo IV Day 1 every 3 weeks for 4 doses.&#xD;
Followed 2-3 weeks later by Doxorubicin (A) 60 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles OR Epirubicin (E) 90 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles.&#xD;
+ placebo IV Day 1 every 3 weeks for 3 to 4 doses depending on AC/EC schedule used.&#xD;
Approximately 3-4 weeks later: Surgery (Lumpectomy or mastectomy and axillary staging), followed by placebo IV Day 1 every 3 weeks after surgery until 1 year after the first dose.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Following randomization, patients will receive Paclitaxel 80 mg/m2 IV weekly x 12 doses + Carboplatin AUC of 5 IV Day 1 every 3 weeks for 4 cycles + Atezolizumab 1200 mg Day 1 every 3 weeks for 4 doses.&#xD;
Followed 2-3 weeks later by Doxorubicin (A) 60 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles OR Epirubicin (E) 90 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles.&#xD;
+ Atezolizumab 1200 mg Day 1 every 3 weeks for 3 to 4 doses depending on AC/EC schedule used.&#xD;
Approximately 3-4 weeks later: Surgery (Lumpectomy or mastectomy and axillary staging), followed by Atezolizumab 1200 mg Day 1 every 3 weeks after surgery until 1 year after the first dose.</description>
    <arm_group_label>Atezolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The patient must have consented to participate and, prior to beginning specific study&#xD;
             procedures, must have signed and dated an appropriate IRB-approved consent form that&#xD;
             conforms to federal and institutional guidelines for study treatment and for&#xD;
             submission of tumor samples from a research biospy as required by NSABP B-59/GBG&#xD;
             96-GeparDouze for baseline correlative science studies.&#xD;
&#xD;
          -  The diagnosis of invasive adenocarcinoma of the breast must have been made by core&#xD;
             needle biopsy.&#xD;
&#xD;
          -  Local testing on the diagnostic core must have determined the tumor to be ER-negative,&#xD;
             PgR-negative, and HER2-negative by current ASCO/CAP guidelines. (If local testing has&#xD;
             determined a tumor to be HER2 equivocal or to have a borderline ER/PgR status (% IHC&#xD;
             staining &lt; 10% for both) and other eligibility criteria are met, material may be&#xD;
             submitted for central testing to determine eligibility.)&#xD;
&#xD;
          -  Central testing for ER, PgR, and HER2 will be performed, and the tumor must be&#xD;
             determined to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP&#xD;
             Guidelines Recommendations.&#xD;
&#xD;
          -  The tumor specimen used for central ER, PgR, and HER2 testing must also be used for&#xD;
             central testing of PD-L1 status using the Ventana PD-L1 testing result including PD-L1&#xD;
             indeterminate Patients will be classifies as positive, negative, or indeterminate for&#xD;
             stratification purposes.&#xD;
&#xD;
          -  Patients must be ≥ 18 years old.&#xD;
&#xD;
          -  Patient may be female or male.&#xD;
&#xD;
          -  The ECOG performance status must be 0-1.&#xD;
&#xD;
          -  The primary tumor can be clinical stage T2 or T3, if clinically node negative&#xD;
             according to AJCC 7th Edition. If the regional lymph nodes are cN1 and cytologically&#xD;
             or histologically positive or cN2-N3 with or without a biopsy, the primary breast&#xD;
             tumor can be clinically T1c, T2, or T3.&#xD;
&#xD;
          -  Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound,&#xD;
             and/or MRI) within 84 days prior to study entry. If suspicious or abnormal, FNA or&#xD;
             core biopsy is recommended. Findings of these evaluations will be used to define the&#xD;
             nodal status prior to study entry according to the following criteria:&#xD;
&#xD;
               -  Nodal status - negative (Imaging of the axilla is negative; Imaging is suspicious&#xD;
                  or abnormal but the FNA or core biopsy of the questionable node[s] on imaging is&#xD;
                  negative)&#xD;
&#xD;
               -  Nodal status - positive (FNA or core biopsy of the node[s] is cytologically or&#xD;
                  histologically suspicious or positive; Imaging is suspicious or abnormal but FNA&#xD;
                  or core biopsy was not performed.)&#xD;
&#xD;
          -  Patients with synchronous bilateral or multicentric HER2-negative breast cancer are&#xD;
             eligible as long as the highest risk tumor is ER-negative and PgR-negative and meets&#xD;
             stage eligibility criteria. All of the other invasive tumors must also be&#xD;
             HER2-negative by ASCO/CAP Guidelines based on local testing. Central testing to&#xD;
             confirm TNBC status is only required for the highest risk tumor.&#xD;
&#xD;
          -  Blood counts performed within 28 days prior to randomization must meet the following&#xD;
             criteria:&#xD;
&#xD;
               -  ANC must be ≥ 1500/mm3;&#xD;
&#xD;
               -  platelet count must be ≥ 100,000/mm3; and&#xD;
&#xD;
               -  hemoglobin must be ≥10 g/dL.&#xD;
&#xD;
          -  The following criteria for evidence of adequate hepatic function performed within 28&#xD;
             days prior to randomization must be met:&#xD;
&#xD;
               -  total bilirubin must be ≤ ULN for the lab unless the patient has a bilirubin&#xD;
                  elevation &gt; ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome&#xD;
                  involving slow conjugation of bilirubin; and&#xD;
&#xD;
               -  alkaline phosphatase must be ≤ 2.5 x ULN for the lab; and&#xD;
&#xD;
               -  AST and ALT must be ≤ 1.5 x ULN for the lab.&#xD;
&#xD;
          -  Patients with AST or ALT or alkaline phosphatase &gt; ULN are eligible for inclusion in&#xD;
             the study if liver imaging (CT, MRI, abdominal ultrasound, PET-CT, or PET scan)&#xD;
             performed within 28 days prior to randomization does not demonstrate metastatic&#xD;
             disease and the requirements in criterion (just above) are met.&#xD;
&#xD;
          -  Patients with alkaline phosphatase that is &gt; ULN but less than or equal to 2.5 x ULN&#xD;
             or with unexplained bone pain are eligible for inclusion in the study if bone imaging&#xD;
             (bone scan, PET-CT scan, or PET scan) supported by additional studies when indicated&#xD;
             (CT, x-ray, MRI) performed within 28 days prior to randomization does not demonstrate&#xD;
             metastatic disease.&#xD;
&#xD;
          -  Patients with N2 or N3 nodal disease or T3 primary disease must undergo liver and bone&#xD;
             imaging (as described in 4.1.13 and 4.1.14) within 28 days prior to randomization,&#xD;
             irrespective of baseline lab results, and studies must not demonstrate metastatic&#xD;
             disease. Chest imaging with chest x-ray PA and Lateral, CT of the chest, or PET-CT&#xD;
             must also be performed.&#xD;
&#xD;
          -  Creatinine clearance ≥ 50 mL/min (see Section 7.2.1 for instructions regarding&#xD;
             calculation of creatinine clearance) performed within 28 days prior to randomization.&#xD;
&#xD;
          -  PT/INR ≤ ULN within 28 days of randomization. Patients receiving therapeutic&#xD;
             anti-coagulants are not eligible.&#xD;
&#xD;
          -  A serum TSH and AM (morning) cortisol performed within 28 days prior to randomization&#xD;
             to obtain a baseline value. Patients with abnormal TSH or AM cortisol baseline levels&#xD;
             should be further evaluated and managed per institutional standards. Asymptomatic&#xD;
             patients who require initiation or adjustment of medication or are followed without&#xD;
             initiating treatment based on endocrinologist's recommendations are eligible.&#xD;
&#xD;
          -  LVEF assessment must be performed within 42 days prior to randomization. (LVEF&#xD;
             assessment performed by echocardiogram is preferred; however, MUGA scan may be&#xD;
             substituted based on institutional preferences.) The LVEF must be ≥ 55% regardless of&#xD;
             the cardiac imaging facility's lower limit of normal.&#xD;
&#xD;
          -  For women of childbearing potential: agreement to remain abstinent (refrain from&#xD;
             heterosexual intercourse) or use contraceptive methods that result in a failure rate&#xD;
             of &lt; 1% per year during the treatment period and for at least 5 months after the last&#xD;
             dose of atezolizumab/placebo or 12 months after the last dose of chemotherapy.&#xD;
&#xD;
               -  A woman is considered to be of childbearing potential if she is not&#xD;
                  postmenopausal, has not reached a postmenopausal state (≥ 12 continuous months of&#xD;
                  amenorrhea with no identified cause other than menopause), and has not undergone&#xD;
                  surgical sterilization (removal of ovaries and/or uterus).&#xD;
&#xD;
               -  Examples of contraceptive methods with a failure rate of &lt; 1% per year include:&#xD;
                  bilateral tubal ligation; male partner sterilization; hormonal contraceptives&#xD;
                  that inhibit ovulation; hormone-releasing intrauterine devices; copper&#xD;
                  intrauterine devices.&#xD;
&#xD;
               -  The reliability of sexual abstinence should be evaluated in relation to the&#xD;
                  duration of the clinical study and the preferred and usual lifestyle of the&#xD;
                  patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or&#xD;
                  postovulation methods) and withdrawal are not acceptable methods of&#xD;
                  contraception.&#xD;
&#xD;
          -  Patient must be willing and able to comply with scheduled visits, treatment plans,&#xD;
             laboratory tests, and other study procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Excisional biopsy or lumpectomy performed prior to study entry.&#xD;
&#xD;
          -  FNA alone to diagnose the breast cancer.&#xD;
&#xD;
          -  Surgical axillary staging procedure prior to randomization. Exception: FNA or core&#xD;
             biopsy of an axillary node is permitted for any patient. A pre-neoadjuvant therapy&#xD;
             sentinel lymph node biopsy for patients with clinically negative axillary nodes is&#xD;
             prohibited.&#xD;
&#xD;
          -  Definitive clinical or radiologic evidence of metastatic disease.&#xD;
&#xD;
          -  Previous history of contralateral invasive breast cancer. (Patients with synchronous&#xD;
             and/or previous contralateral DCIS or LCIS are eligible.)&#xD;
&#xD;
          -  Previous history of ipsilateral invasive breast cancer or ipsilateral DCIS. (Patients&#xD;
             with synchronous or previous ipsilateral LCIS are eligible.)&#xD;
&#xD;
          -  History of non-breast malignancies (except for in situ cancers treated only by local&#xD;
             excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior&#xD;
             to study entry.&#xD;
&#xD;
          -  Treatment including radiation therapy, chemotherapy, or targeted therapy, for the&#xD;
             currently diagnosed breast cancer prior to randomization.&#xD;
&#xD;
          -  Previous therapy with anthracyclines or taxanes for any malignancy.&#xD;
&#xD;
          -  Cardiac disease (history of and/or active disease) that would preclude the use of the&#xD;
             drugs included in the treatment regimens. This includes but is not confined to:&#xD;
&#xD;
               -  Active cardiac disease: angina pectoris that requires the use of anti-anginal&#xD;
                  medication; ventricular arrhythmias except for benign premature ventricular&#xD;
                  contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not&#xD;
                  controlled with medication; conduction abnormality requiring a pacemaker;&#xD;
                  valvular disease with documented compromise in cardiac function; or symptomatic&#xD;
                  pericarditis.&#xD;
&#xD;
               -  History of cardiac disease: myocardial infarction documented by elevated cardiac&#xD;
                  enzymes or persistent regional wall abnormalities on assessment of left&#xD;
                  ventricular function within 6 months prior to randomization; history of&#xD;
                  documented CHF; or documented cardiomyopathy.&#xD;
&#xD;
          -  Uncontrolled hypertension defined as sustained systolic BP &gt; 150 mmHg or diastolic BP&#xD;
             &gt; 90 mmHg. (Patients with initial BP elevations are eligible if initiation or&#xD;
             adjustment of BP medication lowers pressure to meet entry criteria.) Patients&#xD;
             requiring ≥ 3 BP medications are not eligible.&#xD;
&#xD;
          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to&#xD;
             chimeric or humanized antibodies or fusion proteins.&#xD;
&#xD;
          -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to the components of the atezolizumab formulation.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to the components of the doxorubicin, epirubicin,&#xD;
             cyclophosphamide, carboplatin, or paclitaxel formulations.&#xD;
&#xD;
          -  Known allergy or hypersensitivity to liposomal or pegylated G-CSF formulations.&#xD;
&#xD;
          -  Active or history of autoimmune disease or immune deficiency, including but not&#xD;
             limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus&#xD;
             erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid&#xD;
             syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or&#xD;
             multiple sclerosis for a more comprehensive list of autoimmune diseases and immune&#xD;
             deficiencies) with the following exceptions:&#xD;
&#xD;
               -  Patients with a history of autoimmune-related hypothyroidism on a stable dose of&#xD;
                  thyroid replacement hormone may be eligible for this study.&#xD;
&#xD;
               -  Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin&#xD;
                  regimen may be eligible for this study.&#xD;
&#xD;
               -  Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with&#xD;
                  dermatologic manifestations only (e.g., patients with psoriatic arthritis are&#xD;
                  excluded) are permitted provided all of following conditions are met: Rash must&#xD;
                  cover &lt; 10% of body surface area; Disease is well controlled at baseline and&#xD;
                  requires only low-potency topical corticosteroids; No occurrence of acute&#xD;
                  exacerbations of the underlying condition requiring psoralen plus ultraviolet A&#xD;
                  radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors,&#xD;
                  or high-potency or oral corticosteroids within the previous 12 months.&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis&#xD;
             obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active&#xD;
             pneumonitis on screening chest CT scan.&#xD;
&#xD;
          -  Patients known to be HIV positive.&#xD;
&#xD;
          -  Active hepatitis B virus (HBV) infection, defined as having a positive hepatitis B&#xD;
             surface antigen (HBsAg) test at screening. Patients with a past or resolved HBV&#xD;
             infection, defined as having a negative HBsAg test and a positive total hepatitis B&#xD;
             core antibody (HBcAb) test at screening, are eligible for the study if active HBV&#xD;
             infection is ruled out on the basis of HBV DNA viral load per local guidelines.&#xD;
&#xD;
          -  Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody&#xD;
             test at screening confirmed by a polymerase chain reaction (PCR) positive for HCV RNA.&#xD;
&#xD;
          -  Patients with clinically active tuberculosis.&#xD;
&#xD;
          -  Severe infection within 28 days prior to randomization, including but not limited to&#xD;
             hospitalization for complications of infection, bacteremia, or severe pneumonia.&#xD;
&#xD;
          -  Prior allogeneic stem cell or solid organ transplantation.&#xD;
&#xD;
          -  Administration of a live, attenuated vaccine within 28 days prior to randomization or&#xD;
             anticipation that such vaccine will be required during the study. Patients must agree&#xD;
             not to receive live, attenuated influenza vaccine (e.g., FluMist) within 28 days prior&#xD;
             to randomization, during treatment or within 5 months following the last dose of&#xD;
             atezolizumab/placebo.&#xD;
&#xD;
          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical&#xD;
             laboratory finding giving reasonable suspicion of a disease or condition that&#xD;
             contraindicates the use of an investigational drug or that may affect the&#xD;
             interpretation of the results or render the patient at high risk from treatment&#xD;
             complications.&#xD;
&#xD;
          -  Prior treatment with CD137 agonists or immune checkpoint-blockade therapies, including&#xD;
             anti-CD40, anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.&#xD;
&#xD;
          -  Treatment with systemic immunosuppressive medications (including but not limited to&#xD;
             interferons, IL-2) within 28 days or 5 half-lives of the drug, whichever is longer,&#xD;
             prior to randomization.&#xD;
&#xD;
          -  Treatment with systemic immunosuppressive medications (including but not limited to&#xD;
             prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor&#xD;
             necrosis [anti-TNF] factor agents) within 14 days prior to randomization or&#xD;
             anticipation of need for systemic immunosuppressive medications during the study.&#xD;
&#xD;
          -  Nervous system disorder (paresthesias, peripheral motor neuropathy, or peripheral&#xD;
             sensory neuropathy) ≥ Grade 2, per the CTCAE v4.0.&#xD;
&#xD;
          -  Symptomatic peripheral ischemia.&#xD;
&#xD;
          -  Pregnancy or lactation at the time of randomization or intention to become pregnant&#xD;
             during the study. (Note: Negative serum pregnancy test must be obtained within 14 days&#xD;
             prior to randomization).&#xD;
&#xD;
          -  Use of any investigational agent within 28 days prior to randomization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Norman Wolmark, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NSBP Foundation, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of South Alabama Mitchell Cancer Institute</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Katmai Oncology Group</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Bernard's Medical Center</name>
      <address>
        <city>Jonesboro</city>
        <state>Arkansas</state>
        <zip>72401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Bernard's Medical Center</name>
      <address>
        <city>Paragould</city>
        <state>Arkansas</state>
        <zip>72450</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Anaheim</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Baldwin Park</name>
      <address>
        <city>Baldwin Park</city>
        <state>California</state>
        <zip>91706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Bellflower</name>
      <address>
        <city>Bellflower</city>
        <state>California</state>
        <zip>90706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arrowhead Regional Medical Center</name>
      <address>
        <city>Colton</city>
        <state>California</state>
        <zip>92324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Fontana</name>
      <address>
        <city>Fontana</city>
        <state>California</state>
        <zip>92335</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Harbor City</name>
      <address>
        <city>Harbor City</city>
        <state>California</state>
        <zip>90710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Irvine</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer and Blood Specialty Clinic</name>
      <address>
        <city>Los Alamitos</city>
        <state>California</state>
        <zip>90720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Sunset</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-West Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Panorama City</name>
      <address>
        <city>Panorama City</city>
        <state>California</state>
        <zip>91402</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Riverside</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Medical Group</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Zion</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente - Otay</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente- San Marcos</name>
      <address>
        <city>San Marcos</city>
        <state>California</state>
        <zip>92078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope - South Pasadena</name>
      <address>
        <city>South Pasadena</city>
        <state>California</state>
        <zip>91030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Memorial Physician Network</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope - Upland</name>
      <address>
        <city>Upland</city>
        <state>California</state>
        <zip>91786</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PIH Health</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <zip>90602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente-Woodland Hills</name>
      <address>
        <city>Woodland Hills</city>
        <state>California</state>
        <zip>91367</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Comprehensive Cancer Center Aventura</name>
      <address>
        <city>Aventura</city>
        <state>Florida</state>
        <zip>33180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Healthcare System Office of Human Research</name>
      <address>
        <city>Hollywood</city>
        <state>Florida</state>
        <zip>33021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Comprehensive Cancer Center</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Health Cancer Center at Orlando Health</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gwinnett Hospital System Center for Cancer Care</name>
      <address>
        <city>Duluth</city>
        <state>Georgia</state>
        <zip>30096</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gwinnett Hospital System Center for Cancer Care</name>
      <address>
        <city>Lawrenceville</city>
        <state>Georgia</state>
        <zip>30046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gwinnett Hospital System Center for Cancer Care</name>
      <address>
        <city>Snellville</city>
        <state>Georgia</state>
        <zip>30078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care-Bloomington</name>
      <address>
        <city>Bloomington</city>
        <state>Illinois</state>
        <zip>61704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Affiliated Oncologists</name>
      <address>
        <city>Chicago Ridge</city>
        <state>Illinois</state>
        <zip>60415</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John H. Stroger, Jr. Hospital of Cook County</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Specialists of Central Illinois</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Crossroads Cancer Center</name>
      <address>
        <city>Effingham</city>
        <state>Illinois</state>
        <zip>62401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emhurst Memorial Nancy W. Knowles Cancer Center</name>
      <address>
        <city>Elmhurst</city>
        <state>Illinois</state>
        <zip>60126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care-Galesburg</name>
      <address>
        <city>Galesburg</city>
        <state>Illinois</state>
        <zip>61401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edward Cancer Center</name>
      <address>
        <city>Naperville</city>
        <state>Illinois</state>
        <zip>60540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care-Ottawa</name>
      <address>
        <city>Ottawa</city>
        <state>Illinois</state>
        <zip>61350</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care PC</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care-Peru</name>
      <address>
        <city>Peru</city>
        <state>Illinois</state>
        <zip>61354</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edward Cancer Center Plainfield</name>
      <address>
        <city>Plainfield</city>
        <state>Illinois</state>
        <zip>60585</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Specialists of Central Illinois-Swansea</name>
      <address>
        <city>Swansea</city>
        <state>Illinois</state>
        <zip>62226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Medical Oncology and Hematology Inc (W. Jefferson Blvd)</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Medical Oncology and Hematology Inc (Parkview Plaza)</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center Hall-Perrine Cancer Center</name>
      <address>
        <city>Cedar Rapids</city>
        <state>Iowa</state>
        <zip>52403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Chanute</name>
      <address>
        <city>Chanute</city>
        <state>Kansas</state>
        <zip>66720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Dodge City</name>
      <address>
        <city>Dodge City</city>
        <state>Kansas</state>
        <zip>67801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Susan B. Allen Memorial Hosptial</name>
      <address>
        <city>El Dorado</city>
        <state>Kansas</state>
        <zip>67042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center at Mercy - W. Laurel</name>
      <address>
        <city>Independence</city>
        <state>Kansas</state>
        <zip>67301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kingman Community Hospital</name>
      <address>
        <city>Kingman</city>
        <state>Kansas</state>
        <zip>67068</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Medical Center</name>
      <address>
        <city>Liberal</city>
        <state>Kansas</state>
        <zip>67901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McPherson Center for Health</name>
      <address>
        <city>McPherson</city>
        <state>Kansas</state>
        <zip>67460</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newton Medical Center</name>
      <address>
        <city>Newton</city>
        <state>Kansas</state>
        <zip>67114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Labette Health</name>
      <address>
        <city>Parsons</city>
        <state>Kansas</state>
        <zip>67357</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pratt Regional Medical Center</name>
      <address>
        <city>Pratt</city>
        <state>Kansas</state>
        <zip>67124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Salina</name>
      <address>
        <city>Salina</city>
        <state>Kansas</state>
        <zip>67401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas - Wichita</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Kansas</name>
      <address>
        <city>Wichita</city>
        <state>Kansas</state>
        <zip>67214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winfield Healthcare Center</name>
      <address>
        <city>Winfield</city>
        <state>Kansas</state>
        <zip>67156</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute-Downtown</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute-Norton Healthcare Pavilion</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville-James Graham Brown Cancer Center</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Health Louisville; Consultants in Blood Disorders and Cancer</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute-St Matthews</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute-Brownsboro</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40241</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Medical Center-Kenner</name>
      <address>
        <city>Kenner</city>
        <state>Louisiana</state>
        <zip>70065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Jefferson Medical Center Cancer Center</name>
      <address>
        <city>Marrero</city>
        <state>Louisiana</state>
        <zip>70072</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medical Center New Orleans</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Medical Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greater Baltimore Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medstar Union Memorial Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harry and Jeanette Weinberg Cancer Center at Franklin Square</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology - Hematology Brandywine</name>
      <address>
        <city>Brandywine</city>
        <state>Maryland</state>
        <zip>20613</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology - Hematology PA</name>
      <address>
        <city>Columbia</city>
        <state>Maryland</state>
        <zip>21044</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology - Hematology Frederick</name>
      <address>
        <city>Frederick</city>
        <state>Maryland</state>
        <zip>21702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meritus Center for Clinical Research</name>
      <address>
        <city>Hagerstown</city>
        <state>Maryland</state>
        <zip>21742</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology - Hematology PA</name>
      <address>
        <city>Lanham</city>
        <state>Maryland</state>
        <zip>20706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital Hematology Oncology Associates</name>
      <address>
        <city>Silver Spring</city>
        <state>Maryland</state>
        <zip>20904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital</name>
      <address>
        <city>Silver Spring</city>
        <state>Maryland</state>
        <zip>20910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland, St. Joseph Medical Center</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maryland Oncology Hematology</name>
      <address>
        <city>Wheaton</city>
        <state>Maryland</state>
        <zip>20902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Berkshire Hematology Oncology Services at Berkshire Medical Center Cancer and Infusion Center</name>
      <address>
        <city>Pittsfield</city>
        <state>Massachusetts</state>
        <zip>01201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Cancer Institute Brownstown</name>
      <address>
        <city>Brownstown</city>
        <state>Michigan</state>
        <zip>48183</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Cancer Institute Macomb Hospital</name>
      <address>
        <city>Clinton Township</city>
        <state>Michigan</state>
        <zip>48038</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Medical Center Fairlane</name>
      <address>
        <city>Dearborn</city>
        <state>Michigan</state>
        <zip>48126</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan State University</name>
      <address>
        <city>East Lansing</city>
        <state>Michigan</state>
        <zip>48823</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Allegiance Health</name>
      <address>
        <city>Jackson</city>
        <state>Michigan</state>
        <zip>49201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan State University-Breslin Cancer Center</name>
      <address>
        <city>Lansing</city>
        <state>Michigan</state>
        <zip>48910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Medical Center Columbus</name>
      <address>
        <city>Novi</city>
        <state>Michigan</state>
        <zip>48377</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital W Bloomfield</name>
      <address>
        <city>West Bloomfield</city>
        <state>Michigan</state>
        <zip>48322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Cancer Institute Wyandotte Hospital</name>
      <address>
        <city>Wyandotte</city>
        <state>Michigan</state>
        <zip>48192</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Missouri-Ellis Fischel Cancer Center</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newark Beth Israel Medical Center</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center at Cooper</name>
      <address>
        <city>Voorhees</city>
        <state>New Jersey</state>
        <zip>08043</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Oncology Hematology PC</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broome Oncolgy</name>
      <address>
        <city>Binghamton</city>
        <state>New York</state>
        <zip>13905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broome Oncology</name>
      <address>
        <city>Johnson City</city>
        <state>New York</state>
        <zip>13790</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Health Quest Medical Practice</name>
      <address>
        <city>Poughkeepsie</city>
        <state>New York</state>
        <zip>12601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vassar Brothers Medical Center</name>
      <address>
        <city>Poughkeepsie</city>
        <state>New York</state>
        <zip>12601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RHOA of Cary</name>
      <address>
        <city>Cary</city>
        <state>North Carolina</state>
        <zip>27518</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waverly Hematology Oncology</name>
      <address>
        <city>Cary</city>
        <state>North Carolina</state>
        <zip>27518</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolinas Medical Center-Levine Cancer Insitute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Levine Cancer Center Institute Pineville</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RHOA of Garner</name>
      <address>
        <city>Garner</city>
        <state>North Carolina</state>
        <zip>27529</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNC Regional Physicians Hematology and Oncolgoy</name>
      <address>
        <city>High Point</city>
        <state>North Carolina</state>
        <zip>27262</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FirstHealth of the Carolinas FirstHealth Outpatient Cancer Center</name>
      <address>
        <city>Pinehurst</city>
        <state>North Carolina</state>
        <zip>28374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rex Cancer Center</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RHOA of Blue Ridge</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RCC of Wakefield</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nash UNC Health Care - Danny Talbott Cancer Center</name>
      <address>
        <city>Rocky Mount</city>
        <state>North Carolina</state>
        <zip>28704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Roger Maris Cancer Center</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aultman Alliance Cancer Center</name>
      <address>
        <city>Alliance</city>
        <state>Ohio</state>
        <zip>44601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aultman Hospital</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aultman Medical Group Hematology and Oncology</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Wexner Medical Center-Investigational Drug Service Oncology</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Stephanie Speilman Comprehensive Breast Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willamette Valley Cancer Institute and Research Center</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Northwest-Oncology/Hematology</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists</name>
      <address>
        <city>Tigard</city>
        <state>Oregon</state>
        <zip>97223</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center-Beaver</name>
      <address>
        <city>Beaver</city>
        <state>Pennsylvania</state>
        <zip>15009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center - Passavant North</name>
      <address>
        <city>Cranberry Township</city>
        <state>Pennsylvania</state>
        <zip>16066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ephrata Cancer Center</name>
      <address>
        <city>Ephrata</city>
        <state>Pennsylvania</state>
        <zip>17522</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny Cancer Institute St. Vincent</name>
      <address>
        <city>Erie</city>
        <state>Pennsylvania</state>
        <zip>16505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent Hospital</name>
      <address>
        <city>Erie</city>
        <state>Pennsylvania</state>
        <zip>16544</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Cancer Center Horizon</name>
      <address>
        <city>Farrell</city>
        <state>Pennsylvania</state>
        <zip>16121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellspan Medical Oncology</name>
      <address>
        <city>Gettysburg</city>
        <state>Pennsylvania</state>
        <zip>17325</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center- Mountain View</name>
      <address>
        <city>Greensburg</city>
        <state>Pennsylvania</state>
        <zip>15601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Cancer Center Greenville</name>
      <address>
        <city>Greenville</city>
        <state>Pennsylvania</state>
        <zip>16125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AHN Cancer Institute at Jefferson</name>
      <address>
        <city>Jefferson Hills</city>
        <state>Pennsylvania</state>
        <zip>15025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seechler Family Cancer Center</name>
      <address>
        <city>Lebanon</city>
        <state>Pennsylvania</state>
        <zip>17042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Forbes Regional Hospital</name>
      <address>
        <city>Monroeville</city>
        <state>Pennsylvania</state>
        <zip>15146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center UPMC East-Monroeville</name>
      <address>
        <city>Monroeville</city>
        <state>Pennsylvania</state>
        <zip>15146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center Norwin</name>
      <address>
        <city>N. Huntingdon</city>
        <state>Pennsylvania</state>
        <zip>15642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center New Castle</name>
      <address>
        <city>New Castle</city>
        <state>Pennsylvania</state>
        <zip>16105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>WPAON at AGH</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>WPAON at WPH</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Magee-Women's Hospital of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western Pennsylvania Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPCI Investigational Drug Services</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center @ Passavant - HOA</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center @ Passavant - OHA</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center-Upper Saint Clair</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15243</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Cancer Center Northwest</name>
      <address>
        <city>Seneca</city>
        <state>Pennsylvania</state>
        <zip>16346</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center - Uniontown</name>
      <address>
        <city>Uniontown</city>
        <state>Pennsylvania</state>
        <zip>15401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center-Washington</name>
      <address>
        <city>Washington</city>
        <state>Pennsylvania</state>
        <zip>15301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wexford Health &amp; Wellness Pavilion</name>
      <address>
        <city>Wexford</city>
        <state>Pennsylvania</state>
        <zip>15090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Associates of York</name>
      <address>
        <city>York</city>
        <state>Pennsylvania</state>
        <zip>17403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellspan Health-York Cancer Center Oncology Research</name>
      <address>
        <city>York</city>
        <state>Pennsylvania</state>
        <zip>17403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women's and Infants Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gibbs Cancer Center and Research Institute - Pelham</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29651</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spartanburg Medical Center</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Cancer Center Oncology Clinic</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avera Cancer Institute-Sioux Falls</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avera Cancer Institute</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellmont Cancer Institute</name>
      <address>
        <city>Johnson City</city>
        <state>Tennessee</state>
        <zip>37601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellmont Cancer Institute</name>
      <address>
        <city>Kingsport</city>
        <state>Tennessee</state>
        <zip>37660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dell Seton Medical Center at the University of Texas-Seton Infusion Center</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>72701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology Bedford</name>
      <address>
        <city>Bedford</city>
        <state>Texas</state>
        <zip>76022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology Carrollton</name>
      <address>
        <city>Carrollton</city>
        <state>Texas</state>
        <zip>75010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Methodist Dallas Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Medical City Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology Dallas Presbyterian Hospital</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology Denton</name>
      <address>
        <city>Denton</city>
        <state>Texas</state>
        <zip>76201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology Flower Mound</name>
      <address>
        <city>Flower Mound</city>
        <state>Texas</state>
        <zip>75028</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harris Health System-Smith Clinic</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - McAllen South Second</name>
      <address>
        <city>McAllen</city>
        <state>Texas</state>
        <zip>78503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology Midland Allison Cancer Center</name>
      <address>
        <city>Midland</city>
        <state>Texas</state>
        <zip>79701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology Plano</name>
      <address>
        <city>Plano</city>
        <state>Texas</state>
        <zip>75075</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - The Woodlands</name>
      <address>
        <city>The Woodlands</city>
        <state>Texas</state>
        <zip>77380</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wellmont Medical Associates-Oncology and Hematology</name>
      <address>
        <city>Bristol</city>
        <state>Virginia</state>
        <zip>24201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virginia Cancer Care Specialist</name>
      <address>
        <city>Leesburg</city>
        <state>Virginia</state>
        <zip>20176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centra Lynchburg Hematology Oncology</name>
      <address>
        <city>Lynchburg</city>
        <state>Virginia</state>
        <zip>24501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours Richmond Community Hospital Medical Oncology Associates at Memorial Regional Medical Center</name>
      <address>
        <city>Mechanicsville</city>
        <state>Virginia</state>
        <zip>23116</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours St Francis Medical Center</name>
      <address>
        <city>Midlothian</city>
        <state>Virginia</state>
        <zip>23114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Virginia Regional Cancer Center</name>
      <address>
        <city>Norton</city>
        <state>Virginia</state>
        <zip>24273</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bon Secours Richmond Community Hospital Oncology Associates at St. Mary's Hospital</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MRCC Auburn</name>
      <address>
        <city>Auburn</city>
        <state>Washington</state>
        <zip>98001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MRCC Gig Harbor</name>
      <address>
        <city>Gig Harbor</city>
        <state>Washington</state>
        <zip>98335</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MRCC Puyallup</name>
      <address>
        <city>Puyallup</city>
        <state>Washington</state>
        <zip>98372</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MultiCare Health System</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MultiCare Institute for Research &amp; Innovation</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CAMC Health Education and Research Institute</name>
      <address>
        <city>Charleston</city>
        <state>West Virginia</state>
        <zip>25304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Virginia University</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care-Southern Lakes</name>
      <address>
        <city>Burlington</city>
        <state>Wisconsin</state>
        <zip>53105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Health Center Fond du Lac</name>
      <address>
        <city>Fond Du Lac</city>
        <state>Wisconsin</state>
        <zip>54937</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care-Germantown Health Center</name>
      <address>
        <city>Germantown</city>
        <state>Wisconsin</state>
        <zip>53022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care-Grafton</name>
      <address>
        <city>Grafton</city>
        <state>Wisconsin</state>
        <zip>53024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora BayCare Medical Center</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54311</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care-Kenosha South</name>
      <address>
        <city>Kenosha</city>
        <state>Wisconsin</state>
        <zip>53142</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care-Milwaukee South</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora St. Lukes Medical Center-Pharmacy Only</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora West Allis Medical Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Sinai Medical Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vince Lombardi Cancer Clinic Oshkosh</name>
      <address>
        <city>Oshkosh</city>
        <state>Wisconsin</state>
        <zip>54904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care-Racine</name>
      <address>
        <city>Racine</city>
        <state>Wisconsin</state>
        <zip>53406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vince Lombardi Cancer Clinic Sheboygan</name>
      <address>
        <city>Sheboygan</city>
        <state>Wisconsin</state>
        <zip>53081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Medical Center in Summit</name>
      <address>
        <city>Summit</city>
        <state>Wisconsin</state>
        <zip>53066</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vince Lombardi Cancer Clinic-Two Rivers</name>
      <address>
        <city>Two Rivers</city>
        <state>Wisconsin</state>
        <zip>54241</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Cancer Care</name>
      <address>
        <city>Wauwatosa</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CIUSSS de l'Est-de-l'Ile-de-Montreal-Hopital-Maisonneuve-Rosemont</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H1T2M4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier d'Universite de Montreal CHUM-Hotel Dieu</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2XOA9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SMBD-Jewish General Hospital (MPSG)</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre-Cedars Cancer Centre</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4A3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Quebec-Hospital du Saint-Sacrement</name>
      <address>
        <city>Quebec City</city>
        <state>Quebec</state>
        <zip>G1S4L8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>anti-PD-L1 antibody</keyword>
  <keyword>TNBC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atezolizumab</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03281954
org study id: NSABP B-59/GBG 96-GeparDouze
secondary id: 2017-002771-25
secondary id: MO39875
nct id: NCT03281954
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this study is to learn if the usual chemotherapy given before surgery
      (neoadjuvant therapy) for breast cancer plus the experimental drug, atezolizumab, is better
      than the usual chemotherapy plus a placebo. (A placebo is a drug that looks like the study
      drug but contains no medication.) The usual chemotherapy in this study is paclitaxel (WP) and
      carboplatin followed by doxorubicin and cyclophosphamide (AC) or epirubicin and
      cyclophosphamide (EC). Usually, after neoadjuvant therapy and surgery for triple negative
      breast cancer, no additional treatment is given unless the cancer returns. This study will
      also look at continuing treatment after surgery with atezolizumab or the placebo. To be
      better, atezolizumab given with the neoadjuvant therapy should be better at: 1) decreasing
      the amount of tumor in the breast than the placebo given with the usual chemotherapy and 2)
      decreasing the chance of the cancer from returning after surgery.

      Another purpose of this study is to test the good and bad effects of atezolizumab when added
      to the usual chemotherapy. Atezolizumab may keep your cancer from growing but it can also
      cause side effects.
NSABP B-59/GBG 96-GeparDouze is a prospective, randomized, double-blind, Phase III clinical
      trial. This is a collaborative study being conducted by NSABP Foundation, Inc. in partnership
      with the German Breast Group (GBG), and supported by funding by Genentech, a Member of the
      Roche Group, and F. Hoffmann-La Roche, Ltd.

      In this clinical trial of neoadjuvant and adjuvant administration of atezolizumab/placebo in
      patients with high risk triple-negative breast cancer, the potential incremental efficacy and
      safety of neoadjuvant administration of atezolizumab/placebo with a sequential regimen of
      weekly paclitaxel with every-3-week carboplatin followed immediately by neoadjuvant
      administration of atezolizumab/placebo with AC/EC will be evaluated. Patients will then
      undergo surgery. Following recovery from surgery, patients will initiate approximately 6
      months of adjuvant therapy with atezolizumab/placebo and receive the same investigational
      agent they received pre-operatively. Administration of radiation therapy will be based on
      local standards at the discretion of patients and investigators, but if administered,
      atezolizumab/placebo will be administered concurrently. Adjuvant atezolizumab/placebo may be
      delayed until after completion of radiation therapy per investigator discretion. Patients
      with residual invasive cancer at the time of surgery may receive capecitabine concurrently
      with atezolizumab/placebo in the adjuvant setting per investigator discretion and local
      guidelines. Patients with germline BRCA1 or BRCA2 mutations with residual invasive cancer at
      the time of surgery may receive olaparib in the adjuvant setting per investigator discretion
      and local guidelines. Patients receiving olaparib must discontinue atezolizumab/placebo.

      The primary aims of the study are 1) to determine value of atezolizumab in improving
      pathologic complete response in the breast and post-therapy lymph nodes evaluated
      histologically (pCR breast and nodes [(ypT0/Tis ypN0)]), and 2) to determine the value of
      atezolizumab in improving event-free survival (EFS). Secondary aims include: pathologic
      complete response in the breast (ypT0/Tis); pathologic complete response in the breast and
      lymph nodes (ypT0 ypN0); positive nodal status conversion rate; overall survival;
      recurrence-free interval: distant disease-free survival; brain metastases free survival; and
      toxicity. The stratification factors for the study are: 1) clinical size of the primary tumor
      (1.1-3.0 cm; > 3.0 cm); 2) nodal status as determined by protocol-specified criteria
      (negative, positive); 3) AC/EC (every 2 weeks; every 3 weeks); and 4) Region (North America;
      Europe).

      For patient eligibility, local testing on the diagnostic core must have determined the
      patient's tumor to be ER-negative, PgR-negative, and HER2-negative by current ASCO/CAP
      guidelines. Material from either the diagnostic core biopsy or the research biopsy must be
      sent for central testing for confirmation of ER, PgR, and HER2 to confirm eligibility. If
      local testing has determined a tumor to be HER2 equivocal or to have a borderline ER/PgR
      status (% IHC staining < 10% for both), material may be submitted for central testing to
      determine eligibility.

      In order to proactively identify and further assess any cardiac toxicity that may occur with
      the combination of anthracyclines and atezolizumab, this study includes a cardiac safety
      lead-in for the first 60 patients who initiate AC/EC. The safety lead-in will consist of
      assessment of ECG and serum troponin-T obtained just prior to administration of the first
      dose of AC/EC, following completion of the administration of the 1st and 3rd cycle of AC/EC
      prior to initiation of the atezolizumab/placebo. An additional assessment of LVEF with
      echocardiogram or MUGA scan will also be obtained prior to the 3rd dose of AC/EC. In order to
      provide an early assessment of cardiac safety, results of the troponin-T assessments, ECGs,
      LVEF assessment, and cardiac safety data will be evaluated by the Data Safety Monitoring
      Board (DSMB) when the last of the initial 20 patients who initiate AC/EC undergo their
      scheduled post-surgery LVEF assessment. When the last of the first 60 patients to initiate
      AC/EC undergo their scheduled post-surgery LVEF assessment, results of the troponin
      assessments, ECGs, LVEF assessments, and cardiac safety data from all 60 patients will be
      evaluated by the DSMB.

      Research core biopsies of breast primary at baseline and 1-4 days prior to the second dose of
      atezolizumab/placebo are a study requirement for all patients. One to three representative
      blocks of residual primary tumor containing the maximum amount of tumor and node with the
      largest focus of metastasis is required from the definitive breast surgery if gross residual
      disease is greater than or equal to 1.0 cm. If gross residual disease is less than 1.0 cm,
      tissue should be submitted, if possible. Blood specimens will be collected on all patients at
      baseline for exploratory biomarker analysis and to support future correlative studies.

      Accrual to NSABP B-59/GBG 96-GeparDouze began in December 2017 and was completed in May 2021
      with a total of 1550 patients randomized. Based on actual accrual and the decision to
      eliminate pCR as a co-primary endpoint, we recalculated the power to detect a hazard ratio of
      0.70 attributed to the addition of atezolizumab, assuming a lost-to-follow-up rate of 0.00083
      per month, using the actual accrual pattern for the power calculation. With 1550 patients
      accrued in 42 months, an additional 22 months follow up will allow us to obtain 252 events
      under the assumptions stated above, which will provide 80% power to detect a HR of 0.7
      between the atezolizumab and the placebo arm at an overall 2-sided alpha level of 0.05.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Event-free survival (EFS)
time frame: From randomization until event, through study follow up to the time target number of events is obtained, up to 5 years
description: Time from randomization until event
measure: Overall survival (OS)
time frame: From date of randomization through study follow-up, to the time the target number of events is obtained, up to 5 years
description: Time from randomization until death from any cause
measure: Pathologic complete response in the breast and lymph nodes (ypT0/Tis ypN0)
time frame: Following completion of neoadjuvant therapy (ypT0/Tis ypN0)
description: Absence of any invasive component in the resected breast specimen and all resected lymph nodes
measure: Distant disease-free survival (DDFS)
time frame: From date of randomization through study follow-up, to the time the target number of events is obtained, up to 5 years
description: Time from randomization until distant recurrence, death from breast cancer, death from other causes, and second primary invasive cancer (non-breast)
measure: Disease-free survival (DFS)
time frame: From the first breast surgical procedure to the first disease recurrence or death from any cause
description: Ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, ipsilateral or contralateral DCIS, second primary non-breast invasive cancer and death attributable to any cause including breast cancer, non-breast cancer, or unknown cause.
measure: Frequency of Adverse Events
time frame: From beginning of study therapy to 90 days after last dose of study therapy
description: Frequency of adverse events graded according to the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
measure: Frequency of immune Adverse Events of Special Interest
time frame: From beginning of study therapy to 90 days after last dose of study therapy
description: Frequency of immune adverse events of special interest according to the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)
measure: Cardiac safety lead-in (Troponin-T)
time frame: prior to initial dose of AC/EC following completion of carboplatin/paclitaxel co-administered with atezolizumab/placebo, approximately 12 weeks
description: Troponin-T levels in blood prior to initial dose of AC/EC following completion of carboplatin/paclitaxel co-administered with atezolizumab/placebo
measure: Cardiac safety lead-in (Troponin-T)
time frame: After administration of the 1st dose of AC/EC prior to administration of atezolizumab/placebo, approximately 1 hour after beginning the 1st dose of AC/EC
description: Troponin-T levels in blood after administration of the 1st cycle of AC/EC prior to administration of atezolizumab/placebo
measure: Cardiac safety lead-in (Troponin-T)
time frame: After administration of the 3rd dose (Cycle 3; each cycle is 21 days) of AC/EC prior to administration of atezolizumab/placebo, approximately 1 hour after beginning the 3rd dose of AC/EC
description: Troponin-T levels in blood after administration of the 3rd cycle of AC/EC prior to administration of atezolizumab/placebo
measure: Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)
time frame: Prior to initiation of carboplatin/paclitaxel and atezolizumab/placebo, at baseline
description: LVEF levels measured at baseline prior to initiation of carboplatin/paclitaxel and atezolizumab/placebo
measure: Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)
time frame: Prior to the 3rd cycle (each cycle is every 21 days) of AC/EC, approximately 6 weeks after initiation of AC/EC
description: LVEF levels measured before 3rd cycle of AC/EC
measure: Cardiac safety lead-in (Left ventricular ejection fraction; LVEF)
time frame: Four to 6 weeks after surgery
description: LVEF levels measured after surgery
arm group label: Placebo
arm group type: Placebo Comparator
description: IV infusion once every 3 weeks for 4 doses (Cycle 1), once every 3 weeks for 4 doses (Cycle 2) and once every 3 weeks after surgery for 1 year after first dose
arm group label: Atezolizumab
arm group type: Experimental
description: IV infusion, 1200mg, once every 3 weeks for 4 doses (Cycle 1), once every 3 weeks for 4 doses (Cycle 2) and once every 3 weeks after surgery for 1 year after first dose
intervention type: Drug
intervention name: Placebo
description: Following randomization, patients will receive Paclitaxel 80 mg/m2 IV weekly x 12 doses + Carboplatin AUC of 5 IV Day 1 every 3 weeks for 4 cycles + placebo IV Day 1 every 3 weeks for 4 doses.
Followed 2-3 weeks later by Doxorubicin (A) 60 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles OR Epirubicin (E) 90 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles.
+ placebo IV Day 1 every 3 weeks for 3 to 4 doses depending on AC/EC schedule used.
Approximately 3-4 weeks later: Surgery (Lumpectomy or mastectomy and axillary staging), followed by placebo IV Day 1 every 3 weeks after surgery until 1 year after the first dose.
arm group label: Placebo
intervention type: Drug
intervention name: Atezolizumab
description: Following randomization, patients will receive Paclitaxel 80 mg/m2 IV weekly x 12 doses + Carboplatin AUC of 5 IV Day 1 every 3 weeks for 4 cycles + Atezolizumab 1200 mg Day 1 every 3 weeks for 4 doses.
Followed 2-3 weeks later by Doxorubicin (A) 60 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles OR Epirubicin (E) 90 mg/m2 IV + cyclophosphamide (C) 600 mg/m2 IV Day 1 every 2 or 3 weeks for 4 cycles.
+ Atezolizumab 1200 mg Day 1 every 3 weeks for 3 to 4 doses depending on AC/EC schedule used.
Approximately 3-4 weeks later: Surgery (Lumpectomy or mastectomy and axillary staging), followed by Atezolizumab 1200 mg Day 1 every 3 weeks after surgery until 1 year after the first dose.
arm group label: Atezolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Norman Wolmark, MD
role: Principal Investigator
affiliation: NSBP Foundation, Inc.
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Atezolizumab