<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/NCT03263650</url>
  </required_header>
  <id_info>
    <org_study_id>2017-0133</org_study_id>
    <secondary_id>NCI-2018-01071</secondary_id>
    <secondary_id>2017-0133</secondary_id>
    <nct_id>NCT03263650</nct_id>
  </id_info>
  <brief_title>Study of Olaparib Maintenance Following Cabazitaxel-Carbo in Men With AVPC</brief_title>
  <official_title>Randomized Phase II Study of Olaparib Maintenance Following Cabazitaxel-Carboplatin Induction Chemotherapy in Men With Aggressive Variant Prostate Cancer (AVPC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this clinical research study is to learn if olaparib, when given after treatment&#xD;
      with cabazitaxel, carboplatin, and prednisone, can help to control aggressive variant&#xD;
      prostate cancer (AVPC). The safety of these drugs will also be studied.&#xD;
&#xD;
      This is an investigational study. Cabazitaxel and carboplatin are FDA approved and&#xD;
      commercially available for the treatment of certain types of prostate cancer. Prednisone is&#xD;
      FDA-approved and commercially available as a corticosteroid. Olaparib is FDA approved and&#xD;
      commercially available for the treatment of certain types of ovarian cancer. The combination&#xD;
      of cabazitaxel and carboplatin followed by olaparib in this study is investigational.&#xD;
&#xD;
      The study doctor can describe how the study drugs are designed to work.&#xD;
&#xD;
      Up to 96 participants will be enrolled on this study. All will take part at MD Anderson.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Groups:&#xD;
&#xD;
      If you are found to be eligible to take part in this study, you will be randomly assigned (as&#xD;
      in a roll of dice) to 1 of 2 study groups. This is done because no one knows if one study&#xD;
      group is better, the same, or worse than the other group. You will have a 2 in 3 chance of&#xD;
      being assigned to Group 1 and a 1 in 3 chance of being assigned to Group 2:&#xD;
&#xD;
        -  If you are in Group 1, you will receive olaparib.&#xD;
&#xD;
        -  If you are in Group 2, you will not receive olaparib.&#xD;
&#xD;
      All participants will receive cabazitaxel and carboplatin.&#xD;
&#xD;
      You and the study staff will know to which group you have been assigned.&#xD;
&#xD;
      Study Drug Administration:&#xD;
&#xD;
      Each study cycle is 21 days.&#xD;
&#xD;
      You will receive cabazitaxel by vein over 60 minutes on Day 1 of Cycles 1-6. You will then&#xD;
      receive carboplatin by vein over 60 minutes on Day 1 of Cycles 1-6.&#xD;
&#xD;
      You will take 1 tablet of prednisone by mouth 2 times each day of Cycles 1-6.&#xD;
&#xD;
      You will be given standard drugs to help decrease the risk of side effects (for example,&#xD;
      filgrastim) before and/or after each dose of cabazitaxel and continuing through several days.&#xD;
      Your doctor will describe these drugs to you in more detail, including how they are given and&#xD;
      any side effects you may expect.&#xD;
&#xD;
      If you are in Group 1, you will take tablets of olaparib 2 times by mouth each day starting&#xD;
      on Day 1 of Cycle 7. Swallow the whole tablet or tablets. Do not chew, crush, divide, or&#xD;
      dissolve the tablets. If you vomit shortly after taking your olaparib tablet you can retake a&#xD;
      new dose as long as you can see that the tablet came out whole. You should take the doses at&#xD;
      the same time each day (or within 2 hours of the scheduled times). Do not take the dose if&#xD;
      you forget and it is more than 2 hours since your scheduled time. Take olaparib at least 1&#xD;
      hour after and 2 hours before eating.&#xD;
&#xD;
      If you are in Group 2, you will receive standard of care treatment and follow-up after Cycle&#xD;
      6. The study doctor will tell you more about what this may mean for you.&#xD;
&#xD;
      Length of Treatment:&#xD;
&#xD;
      You will receive carboplatin and cabazitaxel for up to 6 cycles. If you are in Group 1, you&#xD;
      may continue receiving olaparib for as long as the doctor thinks it is in your best interest.&#xD;
      You may no longer be able to take the study drugs if the disease gets worse, if intolerable&#xD;
      side effects occur, or if you are unable to follow study directions.&#xD;
&#xD;
      Your participation on the study will be over after the follow-up visits.&#xD;
&#xD;
      Study Visits:&#xD;
&#xD;
      On Day 1 of Cycles 1-6:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (up to 5 tablespoons) will be drawn for routine tests, biomarker testing, tumor&#xD;
           marker testing, and to measure your PSA level. At some of these visits, this sample will&#xD;
           also be used for CTC testing. You must fast for up to 12 hours before the Cycle 4 visit.&#xD;
&#xD;
        -  Urine will be collected for tumor marker testing.&#xD;
&#xD;
        -  At Cycle 4 only, you will have a bone scan and either MRIs or CT scans to check the&#xD;
           status of the disease.&#xD;
&#xD;
      After Cycle 6, you will have a second tumor biopsy for biomarker testing to compare to the&#xD;
      one taken at screening. The type of biopsy you have will depend on where the disease has&#xD;
      spread and/or what the doctor thinks is in your best interest. The doctor will discuss with&#xD;
      you the type of biopsy you will have.&#xD;
&#xD;
      On Day 1 of Cycle 7:&#xD;
&#xD;
        -  Blood (up to 5 tablespoons) will be drawn to check your testosterone levels, biomarker&#xD;
           testing, and for tumor marker testing.&#xD;
&#xD;
        -  You will have an EKG.&#xD;
&#xD;
        -  You will have a bone scan and either MRIs or CT scans.&#xD;
&#xD;
      On Day 1 of Cycles 8-10:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (up to 5 tablespoons) will be drawn for routine tests, tumor marker testing,&#xD;
           biomarker testing, and to measure your PSA level. At some of these visits, this sample&#xD;
           will also be used for CTC testing.&#xD;
&#xD;
        -  Urine will be collected for tumor marker testing.&#xD;
&#xD;
      After Cycle 10, you will only have study visits every 3 cycles. Beginning on Day 1 of Cycle&#xD;
      13, every 3 cycles (Cycles 13, 16, 19, and so on):&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  Blood (up to 5 tablespoons) will be drawn for routine tests, tumor marker testing,&#xD;
           biomarker testing, and to measure your PSA level. At some of these visits, this sample&#xD;
           will also be used for CTC testing. You must fast for up to 12 hours before the visits at&#xD;
           Cycle 10 and every 3 cycles after that.&#xD;
&#xD;
        -  Urine will be collected for tumor marker testing.&#xD;
&#xD;
        -  You will have a bone scan and either MRIs or CT scans to check the status of the&#xD;
           disease.&#xD;
&#xD;
        -  You will have an EKG.&#xD;
&#xD;
      If you have severe side effects, you may return to the clinic more often so the study doctor&#xD;
      can check on your health.&#xD;
&#xD;
      End of Study Visit:&#xD;
&#xD;
      When you leave the study, the following tests and procedures will be performed:&#xD;
&#xD;
        -  You will have a physical exam.&#xD;
&#xD;
        -  You will have a bone scan and either MRIs or CT scans to check the status of the&#xD;
           disease.&#xD;
&#xD;
        -  You will have an EKG.&#xD;
&#xD;
        -  Blood (about 3 tablespoons) will be drawn for routine tests, tumor marker testing, and&#xD;
           to measure your PSA level. You must fast for up to 12 hours before this visit.&#xD;
&#xD;
        -  Urine will be collected for tumor marker testing.&#xD;
&#xD;
      Follow-Up:&#xD;
&#xD;
      About every 6 months after the end-of-study visit, the study staff will check your health.&#xD;
      This will be done either by a chart review or a phone call. If you are called, this call will&#xD;
      last about 5 minutes. These calls will stop if you withdraw from the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 3, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>All participants will receive 6 cycles of cabazitaxel and carboplatin before being randomized 2:1 to olaparib maintenance versus observation.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival (PFS) of men with AVPC treated with 6 cycles of cabazitaxel + carboplatin followed by olaparib maintenance versus observation</measure>
    <time_frame>Up to one year from time of randomization</time_frame>
    <description>Progression Free Survival (PFS) calculated as the time from randomization until any one of the following events occurs, whichever comes first:&#xD;
Documented disease progression&#xD;
Start of a new therapy in the absence of progression&#xD;
Death in the absence of progression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Genomic alterations in DNA damage repair (DDR) pathway genes induced and/or selected by carboplatin and cabazitaxel chemotherapy [biopsy #2 vs biopsy #1]: Association with clinical outcome (PFS&gt;6 months)</measure>
    <time_frame>Up to one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of adverse events possibly, probably or definitely attributable to olaparib following cabazitaxel plus carboplatin in men with AVPC</measure>
    <time_frame>Up to one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) of men with AVPC treated with 6 cycles of cabazitaxel + carboplatin followed by olaparib maintenance vs observation</measure>
    <time_frame>Up to one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response evaluation criteria in solid tumors (RECIST) and prostate specific antigen (PSA) response rate (RR) to cabazitaxel + carboplatin induction, and to olaparib maintenance in men with AVPC</measure>
    <time_frame>Up to one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between DDR pathway gene expression changes following carboplatin + cabazitaxel chemotherapy and clinical outcome (PFS&gt;6 months)</measure>
    <time_frame>Up to one year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Collection and archiving of serum, plasma, and urine samples in study patients for later hypothesis generating associations</measure>
    <time_frame>Up to one year</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">119</enrollment>
  <condition>Prostate Cancer Aggressiveness</condition>
  <condition>Prostate Carcinoma</condition>
  <arm_group>
    <arm_group_label>Cabazitaxel + Carboplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cabazitaxel, Cabazitaxel and Carboplatin intravenously on day 1 of cycles 1-6. Prednisone by mouth twice daily on days 1-21 of cycles 1-6.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Olaparib Maintenance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to receive Olaparib by mouth twice daily on Day 1 of cycle 7.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Observation Only</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants randomized to observation only beginning cycle 7.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cabazitaxel</intervention_name>
    <description>25mg/m2 administered intravenously over 60 minutes on day 1 of cycles 1-6; given before carboplatin.</description>
    <arm_group_label>Cabazitaxel + Carboplatin</arm_group_label>
    <other_name>Jevtana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>AUC 4 administered intravenously over 60 minutes on day 1 of cycles 1-6</description>
    <arm_group_label>Cabazitaxel + Carboplatin</arm_group_label>
    <other_name>Paraplatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone 5Mg</intervention_name>
    <description>5 mg administered by mouth twice daily on days 1-21 of cycles 1-6.</description>
    <arm_group_label>Cabazitaxel + Carboplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olaparib</intervention_name>
    <description>Administered by mouth twice daily at a dose of 300 mg by mouth twice daily, dispensed on Day 1 of cycle 7 to participants randomized to receive olaparib maintenance and every 21 days thereafter until the participant completes the study, withdraws from the study or the closure of the study.</description>
    <arm_group_label>Olaparib Maintenance</arm_group_label>
    <other_name>Olaparib Pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of informed consent prior to any study specific procedures.&#xD;
&#xD;
          2. Provision of informed consent for genetic research. If a patient declines to&#xD;
             participate in the genetic research, there will be no penalty or loss of benefit to&#xD;
             the patient. The patient will not be excluded from other aspects of the study&#xD;
             described in this Clinical Study Protocol, so long as they consent to that part.&#xD;
&#xD;
          3. Patients must agree to tissue collection for correlative studies at the specified&#xD;
             timepoints. If patient has undergone a recent tissue collection without intervening&#xD;
             treatment since, that can be retrieved and is deemed of sufficient quantity by the PI&#xD;
             to undertake the proposed correlative studies, it may be used as the baseline.&#xD;
&#xD;
          4. Male aged 18 years and above.&#xD;
&#xD;
          5. Histologically or cytologically confirmed prostate carcinoma.&#xD;
&#xD;
          6. Presence of metastatic disease documented on imaging studies (bone scan, computed&#xD;
             tomography (CT) and/or magnetic resonance imaging (MRI) scans).&#xD;
&#xD;
          7. Patients must meet at least one of the following AVPC criteria: i. Histologically&#xD;
             proven small cell (neuroendocrine) prostate carcinoma ii. Exclusive visceral&#xD;
             metastases. iii. Predominantly lytic bone metastases identified by plain x-ray or CT&#xD;
             scan. iv. Bulky (&gt;/= 5cm in longest dimension) lymphadenopathy or high-grade tumor&#xD;
             mass in prostate/pelvis. v. Low PSA (&lt;/= 10ng/mL) at initial presentation (prior to&#xD;
             androgen ablation or at symptomatic progression in the castrate-setting) plus high&#xD;
             volume (&gt;/= 20) bone metastases. vi. Elevated serum lactate dehydrogenase (&gt;/=2 x&#xD;
             upper limit of normal) or elevated serumcarcinoembryonic antigen (&gt;/= 2 x upper limit&#xD;
             of normal ) in the absence of other etiologies. vii. Short interval (&lt;/= 180 days) to&#xD;
             castrate-resistant progression following initiation of hormonal therapy. viii. Known&#xD;
             loss or mutation (by CLIIA certified molecular testing, IHC and/or DNA sequencing) in&#xD;
             at least 2 of the following: Tp53, RB1 and PTEN.&#xD;
&#xD;
          8. (continued from Inclusion Criteria #7: viiii. Patients who have castration -resistant&#xD;
             disease progression per RECIST but do not meet PCWG3 PSA progression criteria&#xD;
&#xD;
          9. Patients must have documented evidence of progressive disease as defined by any of the&#xD;
             following: a) PSA progression: minimum of 2 rising values (3 measurements) obtained a&#xD;
             minimum of 7 days apart with the last result being at least &gt;/= 1.0 ng/mL; b) New or&#xD;
             increasing non-bone disease (RECIST); c) Positive bone scan with 2 or more new lesions&#xD;
             (PCWG3). d) Increasing symptoms unequivocally attributed to disease progression as&#xD;
             judged by the treating physician and the PI.&#xD;
&#xD;
         10. Surgically or ongoing medically castrated, with baseline testosterone levels of &lt;/= 50&#xD;
             ng/dL &lt;/= 2.0 nM).&#xD;
&#xD;
         11. Eastern Cooperative Oncology Group (ECOG) Performance Status of &lt;/=2.&#xD;
&#xD;
         12. Patients must have normal organ and bone marrow function measured within 7 days prior&#xD;
             to administration of study treatment as defined below: i. Hemoglobin &gt;/= 10.0 g/dL dL&#xD;
             (unless due to bone marrow infiltration by tumor, in which case hemoglobin &gt;/=8gdL is&#xD;
             allowed). Patient may have blood transfusions prior to study enrollment. ii. Absolute&#xD;
             neutrophil count (ANC) &gt;/= 1.5 x 10^9/L (unless due to bone marrow infiltration by&#xD;
             tumor, in which case ANC &gt;1,000/mm3 is allowed) iii. White blood cells (WBC) &gt;3x10^9/L&#xD;
             (unless due to bone marrow infiltration by tumor, in which case WBC &gt;2x109/L is&#xD;
             allowed) iv. No features suggestive of myelodysplastic syndrome/acute myeloid leukemia&#xD;
             on peripheral blood smear v. Platelet count &gt;/= 100 x 10^9/L (unless due to bone&#xD;
             marrow infiltration by tumor, in which case platelet &gt;/=50,000/ mm3 is allowed) vi.&#xD;
             Total bilirubin &lt;/=1.5 x institutional upper limit of normal (ULN) (except for&#xD;
             patients with known Gilbert's disease).&#xD;
&#xD;
         13. (continued from Inclusion Criteria #11 vii. aspartate aminotransferase (serum&#xD;
             glutamine oxaloacetic transminase) and alanine aminotransferase (serum glutamic&#xD;
             pyruvic transaminase) &lt;/= 2.5 x institutional upper limit of normal (unless liver&#xD;
             metastases are present in which case it must be &lt;/= 5x ULN) viii. Calculated&#xD;
             creatinine clearance (Cockcroft-Gault Equation) &gt;/= 40 mL/min.&#xD;
&#xD;
         14. Able to swallow study drugs whole as a tablet/capsule.&#xD;
&#xD;
         15. Patients who have partners of childbearing potential (e.g. female that has not been&#xD;
             surgically sterilized or who are not amenorrheic for &gt;/= 12 months) must be willing to&#xD;
             use a method of birth control in addition to adequate barrier protection as determined&#xD;
             to be acceptable by the investigator during the study and for 13 weeks after last&#xD;
             study drug administration. Please note that the efficacy of hormonal contraception may&#xD;
             be decreased if administered with olaparib.&#xD;
&#xD;
         16. Patient is willing and able to comply with the protocol for the duration of the study&#xD;
             including undergoing treatment and scheduled visits and examinations including follow&#xD;
             up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca&#xD;
             staff and/or staff at MD Anderson)&#xD;
&#xD;
          2. Previous enrolment or randomization in the present study&#xD;
&#xD;
          3. Any prior treatment for castration-resistant prostate cancer (CRPC) with carboplatin,&#xD;
             cisplatin, cabazitaxel or olaparib.&#xD;
&#xD;
          4. Patients whose disease is refractory (defined as evidence of disease progression while&#xD;
             on drug or within 3 months of its discontinuation) to more than 2 lines of&#xD;
             chemotherapy given for CRPC. Any number of chemotherapies to which the patient's&#xD;
             disease is not refractory are allowed, as long as time on treatment did not exceed 6&#xD;
             months (counted from day 1 of cycle 1 to day 1 of the last cycle of treatment).&#xD;
&#xD;
          5. Patients who have not recovered from adverse events secondary to systemic therapy&#xD;
             (except for luteinizing hormone-releasing (LHRH) hormone agonist or antagonist&#xD;
             treatment for prostate cancer, and bisphosphonates or receptor activator of Nf kappa&#xD;
             (RANK) ligand inhibitors for bone strengthening), major surgery or radiotherapy for&#xD;
             the treatment of prostate cancer to a grade &lt;/= 2.&#xD;
&#xD;
          6. Persistent toxicities (&gt;/= common terminology criteria for adverse events grade 2)&#xD;
             with the exception of alopecia, caused by previous cancer therapy.&#xD;
&#xD;
          7. Chronic use of known strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole,&#xD;
             ritonavir, indinavir, saquinavir, telithromycin, clarithromycin, voriconazole,&#xD;
             nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir,&#xD;
             boceprevir, telaprevir and nelfinavir), moderate CYP3A4 inhibitors (e.g. amprenavir,&#xD;
             aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem,&#xD;
             erythromycin, fluconazole, fosamprenavir, imatinib, verapamil), strong CYP3A4 inducers&#xD;
             (e.g. phenytoin, rifampicin, carbamazepine, St.John's Wort, phenobarbital) and&#xD;
             moderate CYP3A4 inducers (e.g. bosentan, efavirenz, etravirine, modafinil and&#xD;
             nafcillin). Concomitant use of these drugs with olaparib is not allowed. Patients may&#xD;
             undergo limited courses of them prior to starting olaparib but will be required to&#xD;
             have &gt;/= 5 week washout period from phenobarbital, and &gt;/=3 week washout period from&#xD;
             the rest, before randomization.&#xD;
&#xD;
          8. Active uncontrolled infection ( patients completing a course of antibiotic or&#xD;
             antiviral therapy whose infection is deemed to be controlled may be allowed on study&#xD;
             after discussion with the PI; the PI will serve as the final arbiter regarding&#xD;
             eligibility).&#xD;
&#xD;
          9. Active or symptomatic viral hepatitis or chronic liver disease.&#xD;
&#xD;
         10. A diagnosis or suspicion of myelodysplastic syndrome/acute myeloid leukemia.&#xD;
&#xD;
         11. A history of pneumonitis or extensive bilateral lung disease of non-malignant&#xD;
             etiology.&#xD;
&#xD;
         12. A malignancy [other than the one treated in this study] which required radiotherapy or&#xD;
             systemic treatment within the past 5 years, or has a &gt;/= 30% probability of recurrence&#xD;
             within 24 months (except for adequately treated non-melanoma skin cancer, curatively&#xD;
             treated in-situ cancer of the Ta urothelial carcinomas).&#xD;
&#xD;
         13. Any underlying medical or psychiatric condition, which in the opinion of the&#xD;
             Investigator, will make the administration of study drug hazardous or obscure the&#xD;
             interpretation of adverse events. Examples include, but are not limited to,&#xD;
             uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction,&#xD;
             superior vena cava syndrome, extensive bilateral lung disease on high-resolution&#xD;
             computed tomography scan, uncontrolled seizures or any psychiatric disorder that&#xD;
             prohibits obtaining informed consent.&#xD;
&#xD;
         14. Patients unable to swallow orally administered medication and patients with&#xD;
             gastrointestinal disorders likely to interfere with absorption of the study&#xD;
             medication.&#xD;
&#xD;
         15. Patients with symptomatic uncontrolled brain metastases or spinal cord compressions. A&#xD;
             scan to confirm the absence of brain metastases is not required. The patient can&#xD;
             receive a stable dose of corticosteroids before and during the study as long as these&#xD;
             were started at least 28 days prior to treatment.&#xD;
&#xD;
         16. Patients with a known hypersensitivity to the olaparib, carboplatin or cabazitaxel.&#xD;
&#xD;
         17. Prisoners or subjects who are involuntarily incarcerated.&#xD;
&#xD;
         18. Subjects who are compulsorily detained for treatment of either a psychiatric or&#xD;
             physical (e.g. infectious disease) illness.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Prostate cancer study: Histologically or cytologically confirmed prostate carcinoma.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ana M. Aparicio, MD</last_name>
    <role>Study Chair</role>
    <affiliation>UT MD Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>M D Anderson Cancer Center</description>
  </link>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>May 1, 2023</last_update_submitted>
  <last_update_submitted_qc>May 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>prostate cancer</keyword>
  <keyword>genomic alterations</keyword>
  <keyword>DNA damage repair</keyword>
  <keyword>DDR pathway gene expression</keyword>
  <keyword>aggressive-variant prostate carcinomas</keyword>
  <keyword>small cell prostate carcinoma</keyword>
  <keyword>neuroendocrine prostate carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Prostatic Neoplasms</mesh_term>
    <mesh_term>Aggression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Olaparib</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/NCT03263650
org study id: 2017-0133
secondary id: NCI-2018-01071
secondary id: 2017-0133
nct id: NCT03263650
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The goal of this clinical research study is to learn if olaparib, when given after treatment
      with cabazitaxel, carboplatin, and prednisone, can help to control aggressive variant
      prostate cancer (AVPC). The safety of these drugs will also be studied.

      This is an investigational study. Cabazitaxel and carboplatin are FDA approved and
      commercially available for the treatment of certain types of prostate cancer. Prednisone is
      FDA-approved and commercially available as a corticosteroid. Olaparib is FDA approved and
      commercially available for the treatment of certain types of ovarian cancer. The combination
      of cabazitaxel and carboplatin followed by olaparib in this study is investigational.

      The study doctor can describe how the study drugs are designed to work.

      Up to 96 participants will be enrolled on this study. All will take part at MD Anderson.
Study Groups:

      If you are found to be eligible to take part in this study, you will be randomly assigned (as
      in a roll of dice) to 1 of 2 study groups. This is done because no one knows if one study
      group is better, the same, or worse than the other group. You will have a 2 in 3 chance of
      being assigned to Group 1 and a 1 in 3 chance of being assigned to Group 2:

        -  If you are in Group 1, you will receive olaparib.

        -  If you are in Group 2, you will not receive olaparib.

      All participants will receive cabazitaxel and carboplatin.

      You and the study staff will know to which group you have been assigned.

      Study Drug Administration:

      Each study cycle is 21 days.

      You will receive cabazitaxel by vein over 60 minutes on Day 1 of Cycles 1-6. You will then
      receive carboplatin by vein over 60 minutes on Day 1 of Cycles 1-6.

      You will take 1 tablet of prednisone by mouth 2 times each day of Cycles 1-6.

      You will be given standard drugs to help decrease the risk of side effects (for example,
      filgrastim) before and/or after each dose of cabazitaxel and continuing through several days.
      Your doctor will describe these drugs to you in more detail, including how they are given and
      any side effects you may expect.

      If you are in Group 1, you will take tablets of olaparib 2 times by mouth each day starting
      on Day 1 of Cycle 7. Swallow the whole tablet or tablets. Do not chew, crush, divide, or
      dissolve the tablets. If you vomit shortly after taking your olaparib tablet you can retake a
      new dose as long as you can see that the tablet came out whole. You should take the doses at
      the same time each day (or within 2 hours of the scheduled times). Do not take the dose if
      you forget and it is more than 2 hours since your scheduled time. Take olaparib at least 1
      hour after and 2 hours before eating.

      If you are in Group 2, you will receive standard of care treatment and follow-up after Cycle
      6. The study doctor will tell you more about what this may mean for you.

      Length of Treatment:

      You will receive carboplatin and cabazitaxel for up to 6 cycles. If you are in Group 1, you
      may continue receiving olaparib for as long as the doctor thinks it is in your best interest.
      You may no longer be able to take the study drugs if the disease gets worse, if intolerable
      side effects occur, or if you are unable to follow study directions.

      Your participation on the study will be over after the follow-up visits.

      Study Visits:

      On Day 1 of Cycles 1-6:

        -  You will have a physical exam.

        -  Blood (up to 5 tablespoons) will be drawn for routine tests, biomarker testing, tumor
           marker testing, and to measure your PSA level. At some of these visits, this sample will
           also be used for CTC testing. You must fast for up to 12 hours before the Cycle 4 visit.

        -  Urine will be collected for tumor marker testing.

        -  At Cycle 4 only, you will have a bone scan and either MRIs or CT scans to check the
           status of the disease.

      After Cycle 6, you will have a second tumor biopsy for biomarker testing to compare to the
      one taken at screening. The type of biopsy you have will depend on where the disease has
      spread and/or what the doctor thinks is in your best interest. The doctor will discuss with
      you the type of biopsy you will have.

      On Day 1 of Cycle 7:

        -  Blood (up to 5 tablespoons) will be drawn to check your testosterone levels, biomarker
           testing, and for tumor marker testing.

        -  You will have an EKG.

        -  You will have a bone scan and either MRIs or CT scans.

      On Day 1 of Cycles 8-10:

        -  You will have a physical exam.

        -  Blood (up to 5 tablespoons) will be drawn for routine tests, tumor marker testing,
           biomarker testing, and to measure your PSA level. At some of these visits, this sample
           will also be used for CTC testing.

        -  Urine will be collected for tumor marker testing.

      After Cycle 10, you will only have study visits every 3 cycles. Beginning on Day 1 of Cycle
      13, every 3 cycles (Cycles 13, 16, 19, and so on):

        -  You will have a physical exam.

        -  Blood (up to 5 tablespoons) will be drawn for routine tests, tumor marker testing,
           biomarker testing, and to measure your PSA level. At some of these visits, this sample
           will also be used for CTC testing. You must fast for up to 12 hours before the visits at
           Cycle 10 and every 3 cycles after that.

        -  Urine will be collected for tumor marker testing.

        -  You will have a bone scan and either MRIs or CT scans to check the status of the
           disease.

        -  You will have an EKG.

      If you have severe side effects, you may return to the clinic more often so the study doctor
      can check on your health.

      End of Study Visit:

      When you leave the study, the following tests and procedures will be performed:

        -  You will have a physical exam.

        -  You will have a bone scan and either MRIs or CT scans to check the status of the
           disease.

        -  You will have an EKG.

        -  Blood (about 3 tablespoons) will be drawn for routine tests, tumor marker testing, and
           to measure your PSA level. You must fast for up to 12 hours before this visit.

        -  Urine will be collected for tumor marker testing.

      Follow-Up:

      About every 6 months after the end-of-study visit, the study staff will check your health.
      This will be done either by a chart review or a phone call. If you are called, this call will
      last about 5 minutes. These calls will stop if you withdraw from the study.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: All participants will receive 6 cycles of cabazitaxel and carboplatin before being randomized 2:1 to olaparib maintenance versus observation.
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free survival (PFS) of men with AVPC treated with 6 cycles of cabazitaxel + carboplatin followed by olaparib maintenance versus observation
time frame: Up to one year from time of randomization
description: Progression Free Survival (PFS) calculated as the time from randomization until any one of the following events occurs, whichever comes first:
Documented disease progression
Start of a new therapy in the absence of progression
Death in the absence of progression
measure: Genomic alterations in DNA damage repair (DDR) pathway genes induced and/or selected by carboplatin and cabazitaxel chemotherapy [biopsy #2 vs biopsy #1]: Association with clinical outcome (PFS>6 months)
time frame: Up to one year
measure: Rate of adverse events possibly, probably or definitely attributable to olaparib following cabazitaxel plus carboplatin in men with AVPC
time frame: Up to one year
measure: Overall survival (OS) of men with AVPC treated with 6 cycles of cabazitaxel + carboplatin followed by olaparib maintenance vs observation
time frame: Up to one year
measure: Response evaluation criteria in solid tumors (RECIST) and prostate specific antigen (PSA) response rate (RR) to cabazitaxel + carboplatin induction, and to olaparib maintenance in men with AVPC
time frame: Up to one year
measure: Association between DDR pathway gene expression changes following carboplatin + cabazitaxel chemotherapy and clinical outcome (PFS>6 months)
time frame: Up to one year
measure: Collection and archiving of serum, plasma, and urine samples in study patients for later hypothesis generating associations
time frame: Up to one year
arm group label: Cabazitaxel + Carboplatin
arm group type: Experimental
description: Cabazitaxel, Cabazitaxel and Carboplatin intravenously on day 1 of cycles 1-6. Prednisone by mouth twice daily on days 1-21 of cycles 1-6.
arm group label: Olaparib Maintenance
arm group type: Experimental
description: Participants randomized to receive Olaparib by mouth twice daily on Day 1 of cycle 7.
arm group label: Observation Only
arm group type: No Intervention
description: Participants randomized to observation only beginning cycle 7.
intervention type: Drug
intervention name: Cabazitaxel
description: 25mg/m2 administered intravenously over 60 minutes on day 1 of cycles 1-6; given before carboplatin.
arm group label: Cabazitaxel + Carboplatin
other name: Jevtana
intervention type: Drug
intervention name: Carboplatin
description: AUC 4 administered intravenously over 60 minutes on day 1 of cycles 1-6
arm group label: Cabazitaxel + Carboplatin
other name: Paraplatin
intervention type: Drug
intervention name: Prednisone 5Mg
description: 5 mg administered by mouth twice daily on days 1-21 of cycles 1-6.
arm group label: Cabazitaxel + Carboplatin
intervention type: Drug
intervention name: Olaparib
description: Administered by mouth twice daily at a dose of 300 mg by mouth twice daily, dispensed on Day 1 of cycle 7 to participants randomized to receive olaparib maintenance and every 21 days thereafter until the participant completes the study, withdraws from the study or the closure of the study.
arm group label: Olaparib Maintenance
other name: Olaparib Pill
criteria: 
gender: Male
gender based: Yes
gender description: Prostate cancer study: Histologically or cytologically confirmed prostate carcinoma.
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ana M. Aparicio, MD
role: Study Chair
affiliation: UT MD Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: M D Anderson Cancer Center
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Prostatic Neoplasms
mesh term: Aggression
mesh term: Prednisone
mesh term: Carboplatin
mesh term: Olaparib