<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/NCT04408118</url>
  </required_header>
  <id_info>
    <org_study_id>MedOPP150</org_study_id>
    <secondary_id>2019-001503-20</secondary_id>
    <nct_id>NCT04408118</nct_id>
  </id_info>
  <brief_title>First Line Atezolizumab, Paclitaxel, and Bevacizumab (Avastin®) in mTNBC</brief_title>
  <acronym>ATRACTIB</acronym>
  <official_title>Phase II Clinical Trial to Evaluate the Efficacy and Safety of First Line Atezolizumab in Combination With Paclitaxel and Bevacizumab (Avastin®) in Patients With Advanced or Metastatic Triple-negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MedSIR</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>MedSIR</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, open-label, single-arm, phase II clinical trial to evaluate to&#xD;
      evaluate the efficacy and safety of first line atezolizumab in combination with paclitaxel&#xD;
      and bevacizumab (Avastin®) in patients with advanced or metastatic triple-negative breast&#xD;
      cancer (mTNBC)&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Men and women age ≥ 18 years with previously untreated unresectable locally advanced or&#xD;
      metastatic triple-negative breast cancer (TNBC) that is not amenable to resection with&#xD;
      curative intent regardless of programmed death-ligand 1 (PD-L1) status.&#xD;
&#xD;
      The number of patients to be included is 100 patients. The primary objective is to evaluate&#xD;
      the efficacy -in terms of progression-free survival (PFS)- of first line atezolizumab in&#xD;
      combination with paclitaxel and bevacizumab (Avastin®) in patients with unresectable locally&#xD;
      advanced or metastatic TNBC.&#xD;
&#xD;
      After signing the ICF and confirmed eligibility, patients will begin treatment on 28 days&#xD;
      cycles: Atezolizumab (840 mg) intravenously on days 1 and 15; Paclitaxel (90 mg/m2) via IV&#xD;
      infusion on days 1, 8 and 15; Bevacizumab (Avastin® 10mg/kg) intravenously on days 1 and 15.&#xD;
&#xD;
      Patients will receive treatment until disease progression, unacceptable toxicity, death, or&#xD;
      discontinuation from the study treatment for any other reason.&#xD;
&#xD;
      Patients discontinuing the study treatment will enter a post- treatment follow-up period&#xD;
      until death, withdrawal of consent, patient is lost to follow-up, or study termination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 5, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS (Progression-free Survival)</measure>
    <time_frame>24 months</time_frame>
    <description>From a clinical point of view, the primary endpoint for this study is the PFS (progression-free survival) defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy (TTR)</measure>
    <time_frame>24 months</time_frame>
    <description>TTR is defined as the time from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a complete response (CR) or partial response (PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy (ORR)</measure>
    <time_frame>24 months</time_frame>
    <description>Objective response rate (ORR) is defined as the sum of CR and PR relative to the number of patients in the analysis set with measurable disease at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy (CBR)</measure>
    <time_frame>24 months</time_frame>
    <description>Clinical benefit rate (CBR) is defined as the proportion of participants with CR, PR or SD ≥24 weeks relative to the number of patients in the analysis set.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy (DoR)</measure>
    <time_frame>24 months</time_frame>
    <description>Duration of response (DoR) is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression, death due to any cause or treatment discontinuation, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy (OS)</measure>
    <time_frame>24 months</time_frame>
    <description>Overall survival (OS) is defined as the time from date of treatment initiation to date of death due to any cause. In the absence of confirmation of death, survival time will be censored to last date the participant was known to be alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy (Best percentage of change of target tumor lesions)</measure>
    <time_frame>24 months</time_frame>
    <description>Best percentage of change from baseline in the size of target tumor lesions is defined as the biggest decrease, or smallest increase if no decrease will be observed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety AEs and SAEs</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence and severity of adverse events (AEs), serious adverse events (SAEs) according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0, including dose reductions, delays, and treatment discontinuations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory objectives (irPFS)</measure>
    <time_frame>24 months</time_frame>
    <description>Immune-related progression-free survival (irPFS) is defined as the period of time from the date of treatment initiation to the date of the first documentation of objective progression of disease (irPD) or death due to any cause in absence of documented irPD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory objectives (irORR)</measure>
    <time_frame>24 months</time_frame>
    <description>Immune-related objective response (irORR) is defined as the proportion of participants with irCR or irPR relative to the number of patients in the analysis set with measurable disease at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exploratory objectives (molecular markers)</measure>
    <time_frame>24 months</time_frame>
    <description>Changes in mutation and copy number in oncogenes, tumor suppressors, and/or other genes associated with disease progression assessed in liquid biopsy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Metastatic Breast Cancer</condition>
  <condition>Advanced Breast Cancer</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All eligible patients will be treated with atezolizumab (840 mg) intravenously on days 1 and 15, Paclitaxel (90 mg/m2) on days 1, 8 and 15 via IV infusion and Bevacizumab (Avastin® 10mg/kg) intravenously on days 1 and 15.&#xD;
Treatment cycles and patient visits are organized in scheduled cycles of 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Atezolizumab (840 mg) will be administered intravenously on Days 1 and 15.&#xD;
The first infusion of atezolizumab will be administered over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.</description>
    <arm_group_label>Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)</arm_group_label>
    <other_name>Paclitaxel</other_name>
    <other_name>Bevacizumab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent form (ICF) prior to participation in any study-related&#xD;
             activities.&#xD;
&#xD;
          2. Male or female patients ≥ 18 years at the time of signing ICF.&#xD;
&#xD;
          3. Ability to comply with the study protocol, in the investigator's judgment.&#xD;
&#xD;
          4. Histologically confirmed TNBC -regardless of PD-L1 status- per American Society of&#xD;
             Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria based on&#xD;
             local testing on the most recent analyzed biopsy. Triple-negative is defined as &lt;1%&#xD;
             expression for estrogen receptor (ER) and progesterone receptor (PgR) as determined by&#xD;
             immunohistochemistry (IHC) and negative for HER2 (0-1+ by immunohistochemistry [IHC]&#xD;
             or 2+ and negative by in situ hybridization [ISH] test).&#xD;
&#xD;
          5. Unresectable locally advanced or metastatic disease documented by computerized&#xD;
             tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to&#xD;
             resection with curative intent.&#xD;
&#xD;
          6. No prior chemotherapy and/or targeted therapy and/or immunotherapy and/or&#xD;
             antiangiogenic agent for MBC. Patients who have received (neo)adjuvant taxane-based&#xD;
             chemotherapy and/or immunotherapy and/or an antiangiogenic agent are required to have&#xD;
             a disease-free interval (DFI) of at least 12 months after completion of each of these&#xD;
             treatments. For (neo)adjuvant non-taxane-based chemotherapy, a DFI of at least 6&#xD;
             months is required.&#xD;
&#xD;
          7. Resolution of all acute toxic effects of prior anti-cancer therapy to grade ≤ 1 as&#xD;
             determined by the NCI-CTCAE v.5.0 (except for alopecia, grade ≤ 2 peripheral&#xD;
             neuropathy, or other toxicities not considered a safety risk for the patient at&#xD;
             investigator's discretion).&#xD;
&#xD;
          8. Evidence of measurable disease or non-measurable disease as per RECIST v.1.1. Patients&#xD;
             with only bone lesions are also eligible.&#xD;
&#xD;
          9. Willingness and ability to provide the most recent tumor biopsy since last progression&#xD;
             from either metastatic or primary tissues at the time of the inclusion to perform&#xD;
             exploratory studies. If not feasible, patient eligibility should be evaluated by a&#xD;
             Sponsor's qualified designee. An additional tumor biopsy from either metastatic or&#xD;
             primary (only if metastatic biopsies cannot be obtained for inaccessible lesion or&#xD;
             subject safety concern) tissues would be collected at disease progression or study&#xD;
             termination whenever it is feasible.&#xD;
&#xD;
             Note: Patients for whom tumor biopsies cannot be obtained (e.g., inaccessible tumor or&#xD;
             safety concern) may submit archived pathological material from either metastatic or&#xD;
             primary sites, but the most recent tumor biopsy from the patient should be obtained&#xD;
             when available.&#xD;
&#xD;
         10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.&#xD;
&#xD;
         11. Life expectancy of ≥12 weeks.&#xD;
&#xD;
         12. Adequate hematologic and organ function within 14 days before the first study&#xD;
             treatment on Cycle 1 Day 1 (C1D1), defined by the following parameters:&#xD;
&#xD;
               1. Hematological: White blood cell (WBC) count &gt; 3.0 x 109/L; Absolute neutrophil&#xD;
                  count (ANC) &gt; 1.5 X 109/L (without granulocyte colony- stimulating factor [G-CSF]&#xD;
                  support within 2 weeks prior to Cycle 1 Day1); Lymphocyte count 3 0.5 x 109/L&#xD;
                  (500μL); Platelet count 3 75.0 x 109/L (without transfusion within 2 weeks prior&#xD;
                  to Cycle 1 Day 1); Hemoglobin &gt; 9.0 g/dL (Patients may be transfused or receive&#xD;
                  erythropoietic treatment to meet this criterion).&#xD;
&#xD;
                  Note: Patients cannot be transfused platelets within 14 days prior to C1D1 to&#xD;
                  meet this criterion. The use of G-CSF within 14 days prior to C1D1 is also&#xD;
                  prohibited.&#xD;
&#xD;
               2. Hepatic: Bilirubin ≤ 1.5 times the upper limit of normal (× ULN) (≤ 3 x ULN in&#xD;
                  the case of Gilbert's disease); aspartate transaminase (AST) and alanine&#xD;
                  transaminase (ALT) ≤ 2.5 × ULN (in the case of liver metastases ≤ 5 × ULN);&#xD;
                  alkaline phosphatase (ALP) ≤ 2.5 × ULN (≤ 5 × ULN in the case of liver and/or&#xD;
                  bone metastases).&#xD;
&#xD;
               3. Serum albumin ≥ 2.5 g/dL&#xD;
&#xD;
               4. Renal: Serum creatinine &lt; 1.5 × ULN or creatinine clearance ≥ 50 mL/min based on&#xD;
                  Cockcroft-Gault glomerular filtration rate estimation. No proteinuria by dipstick&#xD;
                  urinalysis (trace proteinuria is allowed). In cases of proteinuria at least 1+ by&#xD;
                  urinalysis, proteinuria should be less than 500 mg by 24-hour urine collection.&#xD;
&#xD;
               5. Coagulation: For patients not receiving therapeutic anticoagulation: Partial&#xD;
                  Thromboplastin Time (PTT) (or activated Partial Thromboplastin Time [aPTT]) and&#xD;
                  International Normalized Ratio (INR) ≤ 1.5 × ULN. For patients receiving&#xD;
                  therapeutic anticoagulation: stable anticoagulant regimen.&#xD;
&#xD;
         13. Negative human immunodeficiency virus (HIV) test at screening. Patients with a&#xD;
             positive HIV test at screening are eligible provided they are stable on&#xD;
             anti-retroviral therapy, have a CD4 count 3 200/μL, and have an undetectable viral&#xD;
             load.&#xD;
&#xD;
         14. Negative hepatitis B surface antigen (HBsAg) test and negative total hepatitis B core&#xD;
             antibody (HBcAb) tests at screening, or positive total HBcAb test followed by a&#xD;
             negative hepatitis B virus (HBV) DNA test at screening. Current treatment with&#xD;
             anti-viral therapy for HBV is not allowed.&#xD;
&#xD;
             Note: HBV DNA test only to be performed for patients with a positive total HBcAb test.&#xD;
&#xD;
         15. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody&#xD;
             test followed by a negative HCV RNA test at screening.&#xD;
&#xD;
             Note: HCV RNA test only to be performed for patients with a positive HCV antibody&#xD;
             test.&#xD;
&#xD;
         16. Women of childbearing potential must have a negative serum pregnancy test within 14&#xD;
             days before study treatment initiation and agree to remain abstinent (refrain from&#xD;
             heterosexual intercourse) or use one highly effective contraceptive method, or two&#xD;
             effective contraceptive methods, as defined in the protocol during the treatment&#xD;
             period for at least 5 months after the last dose of atezolizumab, and for at least 6&#xD;
             months after the last dose of paclitaxel and bevacizumab (Avastin®).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known active uncontrolled or symptomatic central nervous system (CNS) metastases as&#xD;
             indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients&#xD;
             with a history of CNS metastases are eligible if they meet the following criteria:&#xD;
&#xD;
               -  Evidence of measurable disease or non-measurable disease as per RECIST v.1.1.&#xD;
&#xD;
               -  The patient has no history of intracranial hemorrhage.&#xD;
&#xD;
               -  The patient has not undergone stereotactic radiotherapy within 7 days prior to&#xD;
                  initiation of study treatment, whole-brain radiotherapy within 14 days prior to&#xD;
                  initiation of study treatment, or neurosurgical resection within 28 days prior to&#xD;
                  initiation of study treatment. The patient has no ongoing requirement for&#xD;
                  corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable&#xD;
                  dose is permitted.&#xD;
&#xD;
          2. History of leptomeningeal disease.&#xD;
&#xD;
          3. Uncontrolled tumor-related pain.&#xD;
&#xD;
             Note 1: Patients requiring pain medication must be on a stable regimen at study entry.&#xD;
&#xD;
             Note 2: Symptomatic lesions (e.g., bone metastases or metastases causing nerve&#xD;
             impingement) amenable to palliative radiotherapy should be treated prior to enrolment.&#xD;
             Patients should be recovered from the effects of radiation.&#xD;
&#xD;
          4. 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;
             antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome,&#xD;
             or 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 who are on thyroid&#xD;
                  replacement hormone are eligible for the study.&#xD;
&#xD;
               -  Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen&#xD;
                  are eligible for the study.&#xD;
&#xD;
               -  Patients with eczema, psoriasis, lichen simplex chronicum, or vitiligo with&#xD;
                  dermatologic manifestations only (e.g., patients with psoriatic arthritis are&#xD;
                  excluded) are eligible for the study provided all of following conditions are&#xD;
                  met:&#xD;
&#xD;
               -  Rash must cover &lt; 10% of body surface area.&#xD;
&#xD;
               -  Disease is well controlled at baseline and requires only low-potency topical&#xD;
                  corticosteroids.&#xD;
&#xD;
               -  No occurrence of acute exacerbations of the underlying condition requiring&#xD;
                  psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents,&#xD;
                  oral calcineurin inhibitors, or high potency or oral corticosteroids within the&#xD;
                  previous 12 months.&#xD;
&#xD;
          5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent&#xD;
             drainage procedures.&#xD;
&#xD;
             Note: Patients with indwelling catheters (e.g., PleurX®) are allowed.&#xD;
&#xD;
          6. Uncontrolled or symptomatic hypercalcemia (ionized calcium &gt; 1.5 mmol/L; calcium &gt; 12&#xD;
             mg/dL).&#xD;
&#xD;
          7. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis&#xD;
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of&#xD;
             active pneumonitis on screening chest computed tomography (CT) scan.&#xD;
&#xD;
             Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted.&#xD;
&#xD;
          8. Active tuberculosis.&#xD;
&#xD;
          9. Significant cardiovascular disease 6 months prior to initiation of study treatment.&#xD;
             These include New York Heart Association Class II or greater cardiac disease,&#xD;
             myocardial infarction, unstable arrhythmia, or unstable angina, symptomatic&#xD;
             pericarditis, ventricular arrhythmias - except for benign premature ventricular&#xD;
             contractions-, arrhythmias or conduction abnormalities requiring a pacemaker or not&#xD;
             controlled with medication, and prior peripheral vascular disease including any&#xD;
             cerebrovascular accident including transient ischemic attack, any pulmonary embolism,&#xD;
             any prior deep vein thrombosis, and/or any grade ≥ 2 peripheral vascular disease.&#xD;
&#xD;
         10. Left ventricular ejection fraction (LVEF) &lt; 50% as determined by multiple gated&#xD;
             acquisition (MUGA) scan or echocardiogram (ECHO).&#xD;
&#xD;
         11. Uncontrolled hypertension (systolic blood pressure greater than 160 mmHg and diastolic&#xD;
             blood pressure greater than 100 mmHg).&#xD;
&#xD;
         12. Major surgical procedure (defined as requiring general anesthesia) or significant&#xD;
             traumatic injury within 28 days of start of study drug, or patients who have not&#xD;
             recovered from the side effects of any major surgery.&#xD;
&#xD;
         13. Concurrent malignancy(ies) or malignancy(ies) within 5 years of study enrollment&#xD;
             except for carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I&#xD;
             uterine cancer. For other cancers considered to have a low risk of recurrence,&#xD;
             discussion with the Medical Monitor is required.&#xD;
&#xD;
         14. Treatment with therapeutic oral or IV antibiotics or severe infection 2 weeks prior to&#xD;
             initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to&#xD;
             prevent a urinary tract infection or chronic obstructive pulmonary disease&#xD;
             exacerbation) are eligible for the study.&#xD;
&#xD;
         15. Prior allogeneic stem cell or solid organ transplantation.&#xD;
&#xD;
         16. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study&#xD;
             treatment, or anticipation of need for such a vaccine during atezolizumab treatment or&#xD;
             within 5 months after the final dose of atezolizumab.&#xD;
&#xD;
         17. Extracranial radiotherapy or limited-field palliative radiotherapy within seven days&#xD;
             prior to study enrolment, or patients who have not recovered from radiotherapy-related&#xD;
             toxicities to baseline or grade ≤ 1.&#xD;
&#xD;
         18. Treatment with investigational therapy within 28 days prior to initiation of study&#xD;
             treatment.&#xD;
&#xD;
         19. Treatment with systemic immunosuppressive medication within 2 weeks prior to&#xD;
             initiation of study treatment (including, but not limited to, corticosteroids,&#xD;
             cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-a agents) or&#xD;
             anticipation of need for systemic immunosuppressive medication during study treatment,&#xD;
             with the following exceptions:&#xD;
&#xD;
             Note 1: Patients who have received acute, low-dose systemic immunosuppressant&#xD;
             medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48&#xD;
             hours of corticosteroids for a contrast allergy) are eligible for the study after&#xD;
             Medical Monitor approval has been obtained.&#xD;
&#xD;
             Note 2: Patients who are receiving mineralocorticoids (e.g., fludrocortisone), inhaled&#xD;
             corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or&#xD;
             low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are&#xD;
             eligible for the study.&#xD;
&#xD;
         20. Chronic daily intake of antiplatelet drugs (e.g., aspirin doses of 325 mg/day or&#xD;
             higher or non-steroidal anti-inflammatory medication known to inhibit platelet&#xD;
             function).&#xD;
&#xD;
         21. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies&#xD;
             or&#xD;
&#xD;
         22. Any other concurrent severe and/or uncontrolled medical condition that would, in the&#xD;
             investigator's judgement, contraindicate patient participation in the clinical study.&#xD;
&#xD;
         23. Concurrent participation in other interventional clinical trials.&#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>Antonio Llombart, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MedSIR</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Paula Delgado</last_name>
    <phone>+34 650 728 818</phone>
    <email>paula.delgado@medsir.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Susana Vitorino</last_name>
    <phone>+34656 234 735</phone>
    <email>susana.vitorino@medsir.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hopital Europeen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Celine LE REST</last_name>
    </contact>
    <investigator>
      <last_name>Jacques Medioni, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Klinikum Dessau (MVZ) - Frauenheilkunde</name>
      <address>
        <city>Dessau</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jaqueline Werner</last_name>
    </contact>
    <investigator>
      <last_name>Hermann Voss, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Essen</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Olivier Hoffmann, MD</last_name>
    </contact>
    <investigator>
      <last_name>Oliver Hoomann, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Mannheim</name>
      <address>
        <city>Mannheim</city>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Manuela Reining</last_name>
    </contact>
    <investigator>
      <last_name>Frederik Marme, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori IRCCS Fondazione G. Pascale</name>
      <address>
        <city>Naples</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Istituto Oncologico Veneto IRCCS</name>
      <address>
        <city>Padova</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital de Dénia-MarinaSalud</name>
      <address>
        <city>Dénia</city>
        <state>Alicante</state>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Ribera</name>
      <address>
        <city>Alzira</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital de Sant Joan Despí - Moises Broggi</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Dexeus</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Teresa Alonso</last_name>
      <email>talonso@oncorosell.com</email>
    </contact>
    <investigator>
      <last_name>Alejandro Bueno, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clínico San Cecilio</name>
      <address>
        <city>Granada</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Insular de Gran Canaria</name>
      <address>
        <city>Las Palmas De Gran Canaria</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Arnau de Vilanova</name>
      <address>
        <city>Lleida</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico San Carlos</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Ruber Juan Bravo</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramón y Cajal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario de Navarra</name>
      <address>
        <city>Pamplona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Sant Joan de Reus</name>
      <address>
        <city>Reus</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario San Juan de Alicante</name>
      <address>
        <city>San Juan De Alicante</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Nieves Díaz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocío</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Quirón Valencia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Salvador Blanch, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Barts Health NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sue McCartney</last_name>
    </contact>
    <investigator>
      <last_name>Melissa Phillips, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Cornwall Hospitals Nhs Trust</name>
      <address>
        <city>Truro</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Caroline Goddard</last_name>
    </contact>
    <investigator>
      <last_name>Duncan WHEATLEY, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>United Kingdom</country>
  </location_countries>
  <removed_countries>
    <country>Portugal</country>
  </removed_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>breast cancer</keyword>
  <keyword>metastatic breast cancer</keyword>
  <keyword>triple negative breast cancer</keyword>
  <keyword>HER2 negative</keyword>
  <keyword>HR negative</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>Paclitaxel</mesh_term>
    <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/NCT04408118
org study id: MedOPP150
secondary id: 2019-001503-20
nct id: NCT04408118
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicenter, open-label, single-arm, phase II clinical trial to evaluate to
      evaluate the efficacy and safety of first line atezolizumab in combination with paclitaxel
      and bevacizumab (Avastin®) in patients with advanced or metastatic triple-negative breast
      cancer (mTNBC)
Men and women age ≥ 18 years with previously untreated unresectable locally advanced or
      metastatic triple-negative breast cancer (TNBC) that is not amenable to resection with
      curative intent regardless of programmed death-ligand 1 (PD-L1) status.

      The number of patients to be included is 100 patients. The primary objective is to evaluate
      the efficacy -in terms of progression-free survival (PFS)- of first line atezolizumab in
      combination with paclitaxel and bevacizumab (Avastin®) in patients with unresectable locally
      advanced or metastatic TNBC.

      After signing the ICF and confirmed eligibility, patients will begin treatment on 28 days
      cycles: Atezolizumab (840 mg) intravenously on days 1 and 15; Paclitaxel (90 mg/m2) via IV
      infusion on days 1, 8 and 15; Bevacizumab (Avastin® 10mg/kg) intravenously on days 1 and 15.

      Patients will receive treatment until disease progression, unacceptable toxicity, death, or
      discontinuation from the study treatment for any other reason.

      Patients discontinuing the study treatment will enter a post- treatment follow-up period
      until death, withdrawal of consent, patient is lost to follow-up, or study termination.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PFS (Progression-free Survival)
time frame: 24 months
description: From a clinical point of view, the primary endpoint for this study is the PFS (progression-free survival) defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1.
measure: Efficacy (TTR)
time frame: 24 months
description: TTR is defined as the time from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a complete response (CR) or partial response (PR).
measure: Efficacy (ORR)
time frame: 24 months
description: Objective response rate (ORR) is defined as the sum of CR and PR relative to the number of patients in the analysis set with measurable disease at baseline.
measure: Efficacy (CBR)
time frame: 24 months
description: Clinical benefit rate (CBR) is defined as the proportion of participants with CR, PR or SD ≥24 weeks relative to the number of patients in the analysis set.
measure: Efficacy (DoR)
time frame: 24 months
description: Duration of response (DoR) is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression, death due to any cause or treatment discontinuation, whichever occurs first.
measure: Efficacy (OS)
time frame: 24 months
description: Overall survival (OS) is defined as the time from date of treatment initiation to date of death due to any cause. In the absence of confirmation of death, survival time will be censored to last date the participant was known to be alive.
measure: Efficacy (Best percentage of change of target tumor lesions)
time frame: 24 months
description: Best percentage of change from baseline in the size of target tumor lesions is defined as the biggest decrease, or smallest increase if no decrease will be observed.
measure: Safety AEs and SAEs
time frame: 24 months
description: Incidence and severity of adverse events (AEs), serious adverse events (SAEs) according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0, including dose reductions, delays, and treatment discontinuations.
measure: Exploratory objectives (irPFS)
time frame: 24 months
description: Immune-related progression-free survival (irPFS) is defined as the period of time from the date of treatment initiation to the date of the first documentation of objective progression of disease (irPD) or death due to any cause in absence of documented irPD.
measure: Exploratory objectives (irORR)
time frame: 24 months
description: Immune-related objective response (irORR) is defined as the proportion of participants with irCR or irPR relative to the number of patients in the analysis set with measurable disease at baseline.
measure: Exploratory objectives (molecular markers)
time frame: 24 months
description: Changes in mutation and copy number in oncogenes, tumor suppressors, and/or other genes associated with disease progression assessed in liquid biopsy.
arm group label: Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)
arm group type: Experimental
description: All eligible patients will be treated with atezolizumab (840 mg) intravenously on days 1 and 15, Paclitaxel (90 mg/m2) on days 1, 8 and 15 via IV infusion and Bevacizumab (Avastin® 10mg/kg) intravenously on days 1 and 15.
Treatment cycles and patient visits are organized in scheduled cycles of 28 days.
intervention type: Drug
intervention name: Atezolizumab
description: Atezolizumab (840 mg) will be administered intravenously on Days 1 and 15.
The first infusion of atezolizumab will be administered over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.
arm group label: Atezolizumab + Paclitaxel + Bevacizumab (Avastin®)
other name: Paclitaxel
other name: Bevacizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Antonio Llombart, PhD
role: Principal Investigator
affiliation: MedSIR
last name: Paula Delgado
phone: +34 650 728 818
email: paula.delgado@medsir.org
last name: Susana Vitorino
phone: +34656 234 735
email: susana.vitorino@medsir.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
facility: 
status: Not yet recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
facility: 
status: Not yet recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: France
country: Germany
country: Italy
country: Spain
country: United Kingdom
country: Portugal
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Paclitaxel
mesh term: Atezolizumab