<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/NCT03801369</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00018504</org_study_id>
    <secondary_id>NCI-2019-00388</secondary_id>
    <secondary_id>STUDY00018504</secondary_id>
    <nct_id>NCT03801369</nct_id>
  </id_info>
  <brief_title>Olaparib in Combination With Either Durvalumab, Selumetinib, or Capivasertib or Ceralasertib Alone in Treating Patients With Metastatic Triple Negative Breast Cancer</brief_title>
  <official_title>A Phase II, Open-Label, Study of Olaparib in Combination With Either Durvalumab (MEDI4736), Selumetinib or Capivasertib, or Ceralasertib Monotherapy in Patients With Metastatic Triple-Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>OHSU Knight Cancer Institute</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>
      This phase II study assesses the efficacy of the combination of olaparib with durvalumab,&#xD;
      selumetinib, or capivasertib or ceralasertib alone in the treatment of patients with&#xD;
      metastatic triple negative breast cancer (TNBC). Olaparib may stop growth of tumor cells by&#xD;
      inhibiting some of the enzymes (ADP ribose polymerase [PARP]) needed for cell growth.&#xD;
      Durvalumab, a monoclonal antibody, inhibits the growth and spread of tumors by stimulating&#xD;
      the patient's antitumor immune response. Selumetinib, capivasertib, and ceralasertib are&#xD;
      inhibitor drugs that may stop the growth of tumor cells by blocking some of the enzymes (MEK,&#xD;
      AKT, ATR) needed for cell growth. Giving olaparib together with durvalumab, selumetinib, or&#xD;
      capivasertib or giving ceralasertib alone may provide an effective method to treat patients&#xD;
      with metastatic triple negative breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. Assess overall response to treatment.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Assess participant benefit from treatment. II. Determine the time to disease progression&#xD;
      following response to study therapy.&#xD;
&#xD;
      III. Determine time to first disease progression or death of participants enrolled on the&#xD;
      study.&#xD;
&#xD;
      IV. Determine survival of participants enrolled on the study. V. Assess safety and&#xD;
      tolerability of the proposed therapy.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To assess a change in quality of life (QOL) as measured by European Organization for&#xD;
      Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) in&#xD;
      each treatment arm.&#xD;
&#xD;
      II. To assess a change in QOL as measured by Breast Cancer-Specific Quality of Life&#xD;
      Questionnaire (QLQ-BR23) in each treatment arm.&#xD;
&#xD;
      III. Examine response rates depending on tumor characteristics. IV. Identify predictive&#xD;
      biomarkers of sensitivity to therapy. V. Identify emerging mechanism of resistance to&#xD;
      therapy. VI. Determine changes in tumor cells and the tumor microenvironment induced by PARP&#xD;
      inhibitors.&#xD;
&#xD;
      OUTLINE: This is an open-label, multi-arm phase II study of olaparib in combination with&#xD;
      durvalumab, selumetinib, or capivasertib, or ceralasertib monotherapy.&#xD;
&#xD;
      LEAD IN: Patients with biopsy proven TNBC undergo a pre-treatment biopsy. At the 2 week mark,&#xD;
      patients then undergo a repeat on-treatment biopsy. Patients also receive olaparib orally&#xD;
      (PO) twice daily (BID) on days 1-28 for one cycle. Treatment repeats every 28 days for up to&#xD;
      1 cycle in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      Patients are then assigned to 1 of 4 arms based on predefined molecular tumor&#xD;
      characteristics.&#xD;
&#xD;
      ARM I: Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab&#xD;
      intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up&#xD;
      to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients&#xD;
      deriving clinical benefit from treatment may, at the investigator's discretion and in the&#xD;
      absence of disease progression or unacceptable toxicity, continue on therapy beyond the&#xD;
      planned 13 cycles.&#xD;
&#xD;
      ARM II: Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on&#xD;
      days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence&#xD;
      of disease progression or unacceptable toxicity. Patients deriving clinical benefit from&#xD;
      treatment may, at the investigator's discretion and in the absence of disease progression or&#xD;
      unacceptable toxicity, continue on therapy beyond the planned 13 cycles.&#xD;
&#xD;
      ARM III: Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID&#xD;
      4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles&#xD;
      in the absence of disease progression or unacceptable toxicity. Patients deriving clinical&#xD;
      benefit from treatment may, at the investigator's discretion and in the absence of disease&#xD;
      progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.&#xD;
&#xD;
      ARM IV: Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats&#xD;
      every 28 days for up to 12 cycles in the absence of disease progression or unacceptable&#xD;
      toxicity. Patients deriving clinical benefit from treatment may, at the investigator's&#xD;
      discretion and in the absence of disease progression or unacceptable toxicity, continue on&#xD;
      therapy beyond the planned 13 cycles.&#xD;
&#xD;
      At the completion of all on-study procedures, patients are followed up every 6 months for&#xD;
      disease and survival outcomes up to 1 year. Patients will be asked to submit an optional&#xD;
      tumor biopsy in the event of disease progression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 12, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>End of treatment (Up to 24 months)</time_frame>
    <description>Using the efficacy analysis set, the estimate of ORR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a complete response (CR) or a partial response (PR) that is confirmed on a second scan at least 4 weeks later on the current protocol will be qualified as achieving a response, and will count towards the ORR measurement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate (CBR)</measure>
    <time_frame>End of treatment (Up to 24 months)</time_frame>
    <description>An estimate of CBR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a CR, PR, or stable disease (SD) for at least 6 months on the current protocol will be qualified as deriving benefit from therapy, and will count towards the CBR measurement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>End of treatment (Up to 24 months)</time_frame>
    <description>The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. If a participant dies, irrespective of cause, without documentation of recurrent or progressive disease beforehand, then the date of death will be used to denote the response end date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Progression or death (any cause) up to 1 year post treatment</time_frame>
    <description>PFS is defined as the time after having completed at least one cycle of olaparib monotherapy to the first of either recurrence or relapse (anywhere in the body) or death at the time of last follow-up at 12-months. The estimated distribution of the PFS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Death (any cause) up to 1 year post treatment</time_frame>
    <description>OS is defined as the time after having completed at least one cycle of olaparib monotherapy up to 6 months following the completion of on-study treatment to the date of death or last follow-up at 12 months. The estimated distribution of the OS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of grade 3+ acute toxicity</measure>
    <time_frame>Up to 3 months post treatment</time_frame>
    <description>Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The incidence of having grade 3+ acute toxicity will be determined for participants with triple negative breast cancer (TNBC) that received at least one dose of olaparib and/or durvalumab., selumetinib, capivasertib, or ceralasertib. The 95% confidence interval will be reported with the point estimate of toxicity rate.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in quality of life (QOL) as measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)</measure>
    <time_frame>Baseline to end of treatment (Up to 24 months)</time_frame>
    <description>The QOL measures will be summarized and presented over time graphically using box and spaghetti plots, in addition to summary tables. Mixed effect model will be further used to analyze the longitudinal data. For each instrument, the analysis will include all cycles for which at least 25% of participants in each arm that have an assessment. QLQC30 is a 30-item measure and yields scores for 5 functional scales (physical, role, cognitive, social, and emotional), 3-symptom scales (nausea, pain, and fatigue), a global health and QOL scale, and perceived financial impact of treatment. QLQC30 can distinguish patients according to performance status and is the most commonly used QOL instrument in oncology research. Data from the EORTC QLQ-C30 instrument will be scored as previously described by Aaronson et al.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in QOL as measured by EORTC QLQBR23</measure>
    <time_frame>Baseline to end of treatment (Up to 24 months)</time_frame>
    <description>The QOL measures will be summarized and presented over time graphically using box and spaghetti plots, in addition to summary tables. Mixed effect model will be further used to analyze the longitudinal data. For each instrument, the analysis will include all cycles for which at least 25% of participants in each arm that have an assessment. QLQBR23 is a 23-item instrument that measures symptoms and side effects related to treatment, body image, sexuality, and future perspective specific to breast cancer patients. QLQBR23 has high internal consistency (Cronbach's a = 0.71-0.90), can distinguish between patients based on disease stage, performance status, treatment modality, or prior surgery, and is sensitive to change over time. The EORTC QLQ-BR23 data will be scored as described by the EORTC scoring manual.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">132</enrollment>
  <condition>Anatomic Stage IV Breast Cancer AJCC v8</condition>
  <condition>Metastatic Triple-Negative Breast Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (olaparib, durvalumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (olaparib, selumetinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm III (olaparib, capivasertib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm IV (ceralasertib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>Undergo biopsy</description>
    <arm_group_label>Arm I (olaparib, durvalumab)</arm_group_label>
    <arm_group_label>Arm II (olaparib, selumetinib)</arm_group_label>
    <arm_group_label>Arm III (olaparib, capivasertib)</arm_group_label>
    <arm_group_label>Arm IV (ceralasertib)</arm_group_label>
    <other_name>BIOPSY_TYPE</other_name>
    <other_name>Bx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capivasertib</intervention_name>
    <description>Given PO (orally)</description>
    <arm_group_label>Arm III (olaparib, capivasertib)</arm_group_label>
    <other_name>AZD5363</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ceralasertib</intervention_name>
    <description>Given PO (orally)</description>
    <arm_group_label>Arm IV (ceralasertib)</arm_group_label>
    <other_name>AZD6738</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Given IV (infusion)</description>
    <arm_group_label>Arm I (olaparib, durvalumab)</arm_group_label>
    <other_name>Imfinzi</other_name>
    <other_name>Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer</other_name>
    <other_name>MEDI-4736</other_name>
    <other_name>MEDI4736</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olaparib</intervention_name>
    <description>Given PO (orally)</description>
    <arm_group_label>Arm I (olaparib, durvalumab)</arm_group_label>
    <arm_group_label>Arm II (olaparib, selumetinib)</arm_group_label>
    <arm_group_label>Arm III (olaparib, capivasertib)</arm_group_label>
    <other_name>AZD 2281</other_name>
    <other_name>AZD-2281</other_name>
    <other_name>AZD2281</other_name>
    <other_name>KU-0059436</other_name>
    <other_name>Lynparza</other_name>
    <other_name>PARP Inhibitor AZD2281</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Arm I (olaparib, durvalumab)</arm_group_label>
    <arm_group_label>Arm II (olaparib, selumetinib)</arm_group_label>
    <arm_group_label>Arm III (olaparib, capivasertib)</arm_group_label>
    <arm_group_label>Arm IV (ceralasertib)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selumetinib</intervention_name>
    <description>Given PO (orally)</description>
    <arm_group_label>Arm II (olaparib, selumetinib)</arm_group_label>
    <other_name>ARRY-142886</other_name>
    <other_name>AZD6244</other_name>
    <other_name>MEK Inhibitor AZD6244</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Participants are &gt;= 18 years old at time of informed consent.&#xD;
&#xD;
          -  Metastatic TNBC, as defined by:&#xD;
&#xD;
               -  Estrogen receptor (ER) and progesterone receptor (PR) negative as defined as ER &lt;&#xD;
                  10% and PR &lt; 10% by immunohistochemistry according to American Society of&#xD;
                  Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for&#xD;
                  hormone receptor testing&#xD;
&#xD;
               -  HER2 non-amplified per ASCO/CAP guidelines, defined as:&#xD;
&#xD;
                    -  IHC score 0/1+&#xD;
&#xD;
                    -  IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to&#xD;
                       CEP17 &lt; 2.0, and if reported, average HER2 gene copy number &lt; 4&#xD;
                       signals/cells; or&#xD;
&#xD;
                    -  ISH non-amplified with a ratio of HER2 to CEP17 &lt;2.0, and if reported,&#xD;
                       average HER2 gene copy number &lt; 4 signals/cells&#xD;
&#xD;
          -  Participants with or without germline BRCA mutated TNBC are eligible for study&#xD;
             participation&#xD;
&#xD;
          -  Participants must have at least one measurable site of disease as defined by Response&#xD;
             Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 that is amenable to biopsy&#xD;
&#xD;
          -  Prior therapies for metastatic breast cancer&#xD;
&#xD;
               -  Frontline patients who have not received prior systemic therapy for metastatic&#xD;
                  breast cancer are eligible&#xD;
&#xD;
               -  Patients who have received =&lt; 2 prior chemotherapy regimens for metastatic breast&#xD;
                  cancer are eligible&#xD;
&#xD;
          -  Participants must have fully recovered from the acute toxic effects of all prior&#xD;
             treatment to grade 1 or less, except alopecia which is allowed&#xD;
&#xD;
          -  Participants must have a life expectancy &gt;= 16 weeks&#xD;
&#xD;
          -  Participant must have Eastern Cooperative Oncology Group (ECOG) performance status =&lt;&#xD;
             1&#xD;
&#xD;
          -  Participant must consent to undergo a pre-treatment screening biopsy for enrollment&#xD;
             and subsequent biomarker analyses&#xD;
&#xD;
          -  Participants must consent to undergo one mandatory on-study tumor biopsy following a&#xD;
             2-week induction treatment of olaparib. A second on-study biopsy at time of disease&#xD;
             progression is optional, but not mandatory&#xD;
&#xD;
          -  Participants must not have received previous treatment with PARP inhibitors, including&#xD;
             olaparib&#xD;
&#xD;
          -  Hemoglobin &gt;= 10.0 g/dL (measured within 28 days prior to administration of study&#xD;
             treatment)&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1.5 x 10^9/L (measured within 28 days prior to&#xD;
             administration of study treatment)&#xD;
&#xD;
          -  Platelet count &gt;= 100 x 10^9/L (measured within 28 days prior to administration of&#xD;
             study treatment)&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x institutional upper limit of normal (ULN) (measured within 28&#xD;
             days prior to administration of study treatment)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])&#xD;
             =&lt; 2.5 x institutional upper limit of normal unless liver metastases are present in&#xD;
             which case they must be =&lt; 5 x ULN (measured within 28 days prior to administration of&#xD;
             study treatment)&#xD;
&#xD;
          -  Participants must have creatinine clearance estimated of &gt;= 51 mL/min using the&#xD;
             Cockcroft-Gault equation or based on a 24 hour urine test (measured within 28 days&#xD;
             prior to administration of study treatment)&#xD;
&#xD;
          -  Participants of childbearing potential must have a negative urine or serum pregnancy&#xD;
             test within 28 days of study treatment and confirmed on Day 1 prior to receiving the&#xD;
             first dose of study medication. If the urine test is positive or cannot be confirmed&#xD;
             as negative, a serum pregnancy test will be required&#xD;
&#xD;
          -  Participants of childbearing potential agree to use adequate methods of contraception,&#xD;
             upon signing of informed consent through:&#xD;
&#xD;
               -  6 months after the last dose with olaparib,&#xD;
&#xD;
               -  3 months after the last dose with durvalumab,&#xD;
&#xD;
               -  1 week after the last dose with selumetinib,&#xD;
&#xD;
               -  1 month after the last dose with capivasertib,&#xD;
&#xD;
               -  1 month after the last dose with ceralasertib.&#xD;
&#xD;
        Participants of childbearing potential are those who are not proven postmenopausal.&#xD;
        Postmenopausal is defined as:&#xD;
&#xD;
          -  Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments&#xD;
&#xD;
          -  Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the&#xD;
             post-menopausal range for women under 50&#xD;
&#xD;
          -  Radiation-induced oophorectomy with last menses &gt;1 year ago&#xD;
&#xD;
          -  Chemotherapy-induced menopause with &gt;1 year interval since last menses&#xD;
&#xD;
          -  Surgical sterilization (bilateral oophorectomy or hysterectomy)&#xD;
&#xD;
               -  Sperm-producing participants must use a condom during treatment and for 3 months&#xD;
                  after the last dose of olaparib when having sexual intercourse with a pregnant&#xD;
                  partner or with an individual of childbearing potential. Partners of&#xD;
                  sperm-producing participants should also use a highly effective form of&#xD;
                  contraception if they are of childbearing potential&#xD;
&#xD;
          -  Sperm-producing participants assigned to receive capivasertib must use a condom during&#xD;
             treatment and for 4 months after the last dose of capivasertib when having sexual&#xD;
             intercourse with a pregnant partner or with an individual of childbearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any concurrent anticancer treatment&#xD;
&#xD;
               -  Individuals in the follow-up phase of a prior investigational study may&#xD;
                  participate as long as it has been 4 weeks since last dose of the previous&#xD;
                  investigational agent or device&#xD;
&#xD;
               -  Concurrent use of hormonal therapy for non-cancer related conditions (e.g.,&#xD;
                  hormone replacement therapy) is allowed&#xD;
&#xD;
          -  Participant's with tumors showing androgen receptor (AR) &gt;= 80% by&#xD;
             immunohistochemistry are excluded&#xD;
&#xD;
          -  Other malignancy unless curatively treated with no evidence of disease for &gt;= 5 years&#xD;
             except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer&#xD;
             of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial&#xD;
             carcinoma. Participants with a personal history of treated early stage breast cancer&#xD;
             whose natural history or treatment does not have the potential to interfere with the&#xD;
             safety or efficacy endpoints of the trial, per investigator assessment, are eligible&#xD;
&#xD;
          -  Participants with myelodysplastic syndrome/acute myeloid leukemia or with features&#xD;
             suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)&#xD;
&#xD;
          -  Participant received prior anticancer therapy such as targeted therapies, or systemic&#xD;
             chemotherapy or radiation (except for palliative reasons) within the past 3 weeks, or&#xD;
             5 half-lives, whichever is shorter, prior to first day of treatment&#xD;
&#xD;
          -  Participants with known active central nervous system (CNS) metastases and/or&#xD;
             carcinomatous meningitis&#xD;
&#xD;
               -  Patients with brain metastases may participate provided they do not have&#xD;
                  symptomatic uncontrolled disease. The patient can receive a stable dose of&#xD;
                  corticosteroids before and during the study as long as these were started at&#xD;
                  least 4 weeks prior to treatment. (note: a scan to confirm the absence of brain&#xD;
                  metastases is not required)&#xD;
&#xD;
               -  Patients with spinal cord compression are not eligible unless considered to have&#xD;
                  received definitive treatment for this and evidence of clinically stable disease&#xD;
                  for 28 days&#xD;
&#xD;
               -  Patients with carcinomatous meningitis are not eligible&#xD;
&#xD;
          -  Concomitant use of known strong CYP3A inhibitors (e.g., ketoconazole, posaconazole),&#xD;
             or strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin,&#xD;
             rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate&#xD;
             CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior&#xD;
             to starting study intervention treatment is 5 weeks for enzalutamide or phenobarbital&#xD;
             and 3 weeks for other agents&#xD;
&#xD;
          -  Major surgery within 4 weeks of starting study treatment and patients must have&#xD;
             recovered from any effects of any major surgery&#xD;
&#xD;
          -  Previous allogenic bone marrow transplant or double umbilical cord blood&#xD;
             transplantation (dUCBT)&#xD;
&#xD;
          -  Patients that are immunocompromised, including those with human immunodeficiency virus&#xD;
             (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness are not eligible&#xD;
             for participation&#xD;
&#xD;
               -  Note: HIV-infected participants on effective anti-retroviral therapy with&#xD;
                  undetectable viral load for &gt;= 6 months are eligible for this trial provided that&#xD;
                  there is minimal interactions or overlapping toxicity of the antiretroviral&#xD;
                  therapy with their study intervention. Refer to drug-specific exclusion criteria&#xD;
                  for additional considerations&#xD;
&#xD;
          -  Patients with known active hepatitis (i.e. hepatitis B or C). Refer to drug-specific&#xD;
             exclusion criteria for additional considerations&#xD;
&#xD;
               -  Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen&#xD;
                  (HBsAg) result&#xD;
&#xD;
               -  Patients with a past or resolved HBV infection (defined as the presence of&#xD;
                  hepatitis B core antibody and absence of HBsAg) are eligible&#xD;
&#xD;
               -  Patients positive for hepatitis C virus (HCV) antibody are eligible only if&#xD;
                  polymerase chain reaction (PCR) is negative for HCV RNA. Those with a positive&#xD;
                  HCV PCR will be excluded&#xD;
&#xD;
          -  Participants unable to swallow orally administered medication and participants with&#xD;
             gastrointestinal disorders likely to interfere with absorption of the study medication&#xD;
&#xD;
          -  Participants with visceral crisis defined as severe organ dysfunction as assessed by&#xD;
             signs and symptoms, laboratory studies, and rapid progression of disease&#xD;
&#xD;
          -  Active infection requiring systemic antibiotic therapy. Participants requiring&#xD;
             systemic antibiotics for infection must have completed therapy before treatment is&#xD;
             initiated&#xD;
&#xD;
          -  Participants considered a poor medical risk due to a serious, uncontrolled medical&#xD;
             disorder, non-malignant systemic disease or active, uncontrolled infection. Examples&#xD;
             include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3&#xD;
             months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal&#xD;
             cord compression, superior vena cava syndrome, extensive interstitial bilateral lung&#xD;
             disease on high resolution computed tomography (HRCT) scan or any psychiatric&#xD;
             illness/social situation that prohibits obtaining informed consent&#xD;
&#xD;
          -  Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible&#xD;
             cardiac conditions, as judged by the investigator (e.g., unstable ischemia,&#xD;
             uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval&#xD;
             by Fridericia's correction formula (QTcF) prolongation &gt; 500 ms, electrolyte&#xD;
             disturbances, etc.), or participants with congenital long QT syndrome&#xD;
&#xD;
          -  Participants with a history of hypersensitivity reactions to study agent, olaparib, or&#xD;
             its excipients&#xD;
&#xD;
          -  Participant is pregnant or breastfeeding, or expecting to conceive or father children&#xD;
             within the projected duration of the trial, starting with the screening visit through&#xD;
             120 days after the last dose of trial treatment&#xD;
&#xD;
          -  Sperm-producing participants are prohibited from donating sperm upon signing of&#xD;
             informed consent through:&#xD;
&#xD;
               -  3 months following last dose with olaparib&#xD;
&#xD;
               -  4 months following last dose with capivasertib&#xD;
&#xD;
               -  6 months following last dose with ceralasertib&#xD;
&#xD;
          -  Involvement in the planning and/or conduct of the study&#xD;
&#xD;
          -  Judgment by the investigator that the patient should not participate in the study if&#xD;
             the patient is unlikely to comply with study procedures, restrictions and requirements&#xD;
&#xD;
          -  DRUG-SPECIFIC EXCLUSION CRITERIA: The following criteria require consideration for&#xD;
             participant eligibility to one or more of the available treatment arms. Participant&#xD;
             eligibility may be assessed at the time of initial screening or as part of the&#xD;
             on-study assignment to a specific treatment arm&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: Participant has received prior immunotherapy with&#xD;
             anti-PD-L1, including durvalumab anti-PD-1, anti-CTLA4 or similar drugs in the&#xD;
             metastatic setting&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: Participants may have received prior immunotherapy in&#xD;
             the adjuvant setting, provided&#xD;
&#xD;
               -  No documented disease progression on immunotherapy&#xD;
&#xD;
               -  Treatment with immunotherapy was &gt;1 year from enrollment on study&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: Participant has evidence of interstitial lung disease&#xD;
             or active non-infectious pneumonitis&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: Major surgery within 2 weeks of starting study&#xD;
             treatment and participants must have recovered from any effects of any major surgery&#xD;
&#xD;
               -  Note: Local surgery of isolated lesions for palliative intent is acceptable per&#xD;
                  investigator discretion&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: Active infection including tuberculosis (clinical&#xD;
             evaluation that includes clinical history, physical examination and radiographic&#xD;
             findings, and tuberculosis (TB) testing in line with local practice), hepatitis B&#xD;
             (positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency&#xD;
             virus&#xD;
&#xD;
               -  Participants with a past or resolved HBV infection (defined as the presence of&#xD;
                  hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.&#xD;
&#xD;
               -  Participants positive for hepatitis C (HCV) antibody are eligible only if&#xD;
                  polymerase chain reaction is negative for HCV ribonucleic acid (RNA)&#xD;
&#xD;
               -  Those with controlled human immunodeficiency virus (HIV) are eligible, provided&#xD;
                  that:&#xD;
&#xD;
                    -  Baseline CD4+ T-cell count is &gt;= 200 cells/mm^3, and&#xD;
&#xD;
                    -  HIV plasma viral load is &lt; 60 copies/ml&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: History of active primary immunodeficiency&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: Current or prior use of immunosuppressive medication&#xD;
             within 14 days before the first dose of durvalumab, with the exceptions of intranasal&#xD;
             and inhaled corticosteroids or systemic corticosteroids at physiological doses, which&#xD;
             are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The&#xD;
             following are exceptions to this criterion:&#xD;
&#xD;
               -  Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra&#xD;
                  articular injection)&#xD;
&#xD;
               -  Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of&#xD;
                  prednisone or its equivalent&#xD;
&#xD;
               -  Steroids as premedication for hypersensitivity reactions (e.g., computed&#xD;
                  tomography (CT) scan premedication)&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: Active or prior documented autoimmune or inflammatory&#xD;
             disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease],&#xD;
             diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus,&#xD;
             Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves'&#xD;
             disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are&#xD;
             exceptions to this criterion:&#xD;
&#xD;
               -  Participants with vitiligo or alopecia&#xD;
&#xD;
               -  Participants with hypothyroidism (e.g., following Hashimoto syndrome) stable on&#xD;
                  hormone replacement&#xD;
&#xD;
               -  Any chronic skin condition that does not require systemic therapy&#xD;
&#xD;
               -  Participants without active disease in the last 5 years may be included but only&#xD;
                  after consultation with the study physician&#xD;
&#xD;
               -  Participants with celiac disease controlled by diet alone&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: History of allogenic bone marrow transplant or double&#xD;
             umbilical cord blood transplantation&#xD;
&#xD;
          -  DURVALUMAB EXCLUSION CRITERIA: Participants must not have received live vaccines&#xD;
             within 30 days prior to the first dose of&#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>Alexandra Zimmer, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OHSU Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>OHSU Knight Cancer Institute Clinical Trials</last_name>
      <phone>503-494-7999</phone>
      <email>trials@ohsu.edu</email>
    </contact>
    <investigator>
      <last_name>Alexandra Zimmer, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>August 18, 2023</last_update_submitted>
  <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Alexandra Zimmer</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <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>Durvalumab</mesh_term>
    <mesh_term>Olaparib</mesh_term>
    <mesh_term>Poly(ADP-ribose) Polymerase Inhibitors</mesh_term>
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
    <mesh_term>Immunoglobulin G</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/NCT03801369
org study id: STUDY00018504
secondary id: NCI-2019-00388
secondary id: STUDY00018504
nct id: NCT03801369
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II study assesses the efficacy of the combination of olaparib with durvalumab,
      selumetinib, or capivasertib or ceralasertib alone in the treatment of patients with
      metastatic triple negative breast cancer (TNBC). Olaparib may stop growth of tumor cells by
      inhibiting some of the enzymes (ADP ribose polymerase [PARP]) needed for cell growth.
      Durvalumab, a monoclonal antibody, inhibits the growth and spread of tumors by stimulating
      the patient's antitumor immune response. Selumetinib, capivasertib, and ceralasertib are
      inhibitor drugs that may stop the growth of tumor cells by blocking some of the enzymes (MEK,
      AKT, ATR) needed for cell growth. Giving olaparib together with durvalumab, selumetinib, or
      capivasertib or giving ceralasertib alone may provide an effective method to treat patients
      with metastatic triple negative breast cancer.
PRIMARY OBJECTIVE:

      I. Assess overall response to treatment.

      SECONDARY OBJECTIVES:

      I. Assess participant benefit from treatment. II. Determine the time to disease progression
      following response to study therapy.

      III. Determine time to first disease progression or death of participants enrolled on the
      study.

      IV. Determine survival of participants enrolled on the study. V. Assess safety and
      tolerability of the proposed therapy.

      EXPLORATORY OBJECTIVES:

      I. To assess a change in quality of life (QOL) as measured by European Organization for
      Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) in
      each treatment arm.

      II. To assess a change in QOL as measured by Breast Cancer-Specific Quality of Life
      Questionnaire (QLQ-BR23) in each treatment arm.

      III. Examine response rates depending on tumor characteristics. IV. Identify predictive
      biomarkers of sensitivity to therapy. V. Identify emerging mechanism of resistance to
      therapy. VI. Determine changes in tumor cells and the tumor microenvironment induced by PARP
      inhibitors.

      OUTLINE: This is an open-label, multi-arm phase II study of olaparib in combination with
      durvalumab, selumetinib, or capivasertib, or ceralasertib monotherapy.

      LEAD IN: Patients with biopsy proven TNBC undergo a pre-treatment biopsy. At the 2 week mark,
      patients then undergo a repeat on-treatment biopsy. Patients also receive olaparib orally
      (PO) twice daily (BID) on days 1-28 for one cycle. Treatment repeats every 28 days for up to
      1 cycle in the absence of disease progression or unacceptable toxicity.

      Patients are then assigned to 1 of 4 arms based on predefined molecular tumor
      characteristics.

      ARM I: Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab
      intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up
      to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients
      deriving clinical benefit from treatment may, at the investigator's discretion and in the
      absence of disease progression or unacceptable toxicity, continue on therapy beyond the
      planned 13 cycles.

      ARM II: Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on
      days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence
      of disease progression or unacceptable toxicity. Patients deriving clinical benefit from
      treatment may, at the investigator's discretion and in the absence of disease progression or
      unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

      ARM III: Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID
      4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles
      in the absence of disease progression or unacceptable toxicity. Patients deriving clinical
      benefit from treatment may, at the investigator's discretion and in the absence of disease
      progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

      ARM IV: Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats
      every 28 days for up to 12 cycles in the absence of disease progression or unacceptable
      toxicity. Patients deriving clinical benefit from treatment may, at the investigator's
      discretion and in the absence of disease progression or unacceptable toxicity, continue on
      therapy beyond the planned 13 cycles.

      At the completion of all on-study procedures, patients are followed up every 6 months for
      disease and survival outcomes up to 1 year. Patients will be asked to submit an optional
      tumor biopsy in the event of disease progression.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: End of treatment (Up to 24 months)
description: Using the efficacy analysis set, the estimate of ORR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a complete response (CR) or a partial response (PR) that is confirmed on a second scan at least 4 weeks later on the current protocol will be qualified as achieving a response, and will count towards the ORR measurement.
measure: Clinical benefit rate (CBR)
time frame: End of treatment (Up to 24 months)
description: An estimate of CBR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a CR, PR, or stable disease (SD) for at least 6 months on the current protocol will be qualified as deriving benefit from therapy, and will count towards the CBR measurement.
measure: Duration of response (DOR)
time frame: End of treatment (Up to 24 months)
description: The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. If a participant dies, irrespective of cause, without documentation of recurrent or progressive disease beforehand, then the date of death will be used to denote the response end date.
measure: Progression-free survival (PFS)
time frame: Progression or death (any cause) up to 1 year post treatment
description: PFS is defined as the time after having completed at least one cycle of olaparib monotherapy to the first of either recurrence or relapse (anywhere in the body) or death at the time of last follow-up at 12-months. The estimated distribution of the PFS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.
measure: Overall survival (OS)
time frame: Death (any cause) up to 1 year post treatment
description: OS is defined as the time after having completed at least one cycle of olaparib monotherapy up to 6 months following the completion of on-study treatment to the date of death or last follow-up at 12 months. The estimated distribution of the OS for each treatment will be plotted using Kaplan Meier curves and reported with median survival and 95% confidence intervals if available.
measure: Incidence of grade 3+ acute toxicity
time frame: Up to 3 months post treatment
description: Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. The incidence of having grade 3+ acute toxicity will be determined for participants with triple negative breast cancer (TNBC) that received at least one dose of olaparib and/or durvalumab., selumetinib, capivasertib, or ceralasertib. The 95% confidence interval will be reported with the point estimate of toxicity rate.
measure: Change in quality of life (QOL) as measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
time frame: Baseline to end of treatment (Up to 24 months)
description: The QOL measures will be summarized and presented over time graphically using box and spaghetti plots, in addition to summary tables. Mixed effect model will be further used to analyze the longitudinal data. For each instrument, the analysis will include all cycles for which at least 25% of participants in each arm that have an assessment. QLQC30 is a 30-item measure and yields scores for 5 functional scales (physical, role, cognitive, social, and emotional), 3-symptom scales (nausea, pain, and fatigue), a global health and QOL scale, and perceived financial impact of treatment. QLQC30 can distinguish patients according to performance status and is the most commonly used QOL instrument in oncology research. Data from the EORTC QLQ-C30 instrument will be scored as previously described by Aaronson et al.
measure: Change in QOL as measured by EORTC QLQBR23
time frame: Baseline to end of treatment (Up to 24 months)
description: The QOL measures will be summarized and presented over time graphically using box and spaghetti plots, in addition to summary tables. Mixed effect model will be further used to analyze the longitudinal data. For each instrument, the analysis will include all cycles for which at least 25% of participants in each arm that have an assessment. QLQBR23 is a 23-item instrument that measures symptoms and side effects related to treatment, body image, sexuality, and future perspective specific to breast cancer patients. QLQBR23 has high internal consistency (Cronbach's a = 0.71-0.90), can distinguish between patients based on disease stage, performance status, treatment modality, or prior surgery, and is sensitive to change over time. The EORTC QLQ-BR23 data will be scored as described by the EORTC scoring manual.
arm group label: Arm I (olaparib, durvalumab)
arm group type: Experimental
description: Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.
arm group label: Arm II (olaparib, selumetinib)
arm group type: Experimental
description: Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.
arm group label: Arm III (olaparib, capivasertib)
arm group type: Experimental
description: Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.
arm group label: Arm IV (ceralasertib)
arm group type: Experimental
description: Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.
intervention type: Procedure
intervention name: Biopsy
description: Undergo biopsy
arm group label: Arm I (olaparib, durvalumab)
arm group label: Arm II (olaparib, selumetinib)
arm group label: Arm III (olaparib, capivasertib)
arm group label: Arm IV (ceralasertib)
other name: BIOPSY_TYPE
other name: Bx
intervention type: Drug
intervention name: Capivasertib
description: Given PO (orally)
arm group label: Arm III (olaparib, capivasertib)
other name: AZD5363
intervention type: Drug
intervention name: Ceralasertib
description: Given PO (orally)
arm group label: Arm IV (ceralasertib)
other name: AZD6738
intervention type: Biological
intervention name: Durvalumab
description: Given IV (infusion)
arm group label: Arm I (olaparib, durvalumab)
other name: Imfinzi
other name: Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer
other name: MEDI-4736
other name: MEDI4736
intervention type: Drug
intervention name: Olaparib
description: Given PO (orally)
arm group label: Arm I (olaparib, durvalumab)
arm group label: Arm II (olaparib, selumetinib)
arm group label: Arm III (olaparib, capivasertib)
other name: AZD 2281
other name: AZD-2281
other name: AZD2281
other name: KU-0059436
other name: Lynparza
other name: PARP Inhibitor AZD2281
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Arm I (olaparib, durvalumab)
arm group label: Arm II (olaparib, selumetinib)
arm group label: Arm III (olaparib, capivasertib)
arm group label: Arm IV (ceralasertib)
other name: Quality of Life Assessment
intervention type: Drug
intervention name: Selumetinib
description: Given PO (orally)
arm group label: Arm II (olaparib, selumetinib)
other name: ARRY-142886
other name: AZD6244
other name: MEK Inhibitor AZD6244
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexandra Zimmer, M.D.
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Alexandra Zimmer
investigator title: Principal Investigator
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
mesh term: Durvalumab
mesh term: Olaparib
mesh term: Poly(ADP-ribose) Polymerase Inhibitors
mesh term: Immunoglobulins
mesh term: Antibodies, Monoclonal
mesh term: Immunoglobulin G