<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/NCT03810105</url>
  </required_header>
  <id_info>
    <org_study_id>18-480</org_study_id>
    <nct_id>NCT03810105</nct_id>
  </id_info>
  <brief_title>A Study of Olaparib and Durvalumab in Prostate Cancer</brief_title>
  <official_title>A Phase II Study of Olaparib and Durvalumab in Men With Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer Harboring Mutations in DNA Damage Repair</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if the combination of olaparib and durvalumab are&#xD;
      better than the standard of care for treating prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 7, 2019</start_date>
  <completion_date type="Actual">July 6, 2023</completion_date>
  <primary_completion_date type="Actual">July 6, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Therapeutic efficacy as defined by number of participants with an undetectable PSA</measure>
    <time_frame>1 year</time_frame>
    <description>To assess the therapeutic efficacy as defined by an undetectable PSA (&lt;0.05 or PSA &lt;0.10 for institutions where this is the lower limit of detection) with non-castrate levels of testosterone using the combination olaparib (PARP inhibition) with durvalumab (PDL1 inhibition) at 24 months (cycle 24) in biochemically recurrent prostate cancer</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Castration Sensitive Biochemically Recurrent Prostate Cancer</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olaparib</intervention_name>
    <description>Olaparib 300mg twice daily (600mg total daily dose)</description>
    <arm_group_label>Castration Sensitive Biochemically Recurrent Prostate Cancer</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab 1500mg IV monthly</description>
    <arm_group_label>Castration Sensitive Biochemically Recurrent Prostate Cancer</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to provide written informed consent and HIPAA authorization for the&#xD;
             release of personal health information. A signed informed consent must be obtained&#xD;
             before screening procedures are performed.&#xD;
&#xD;
        NOTE: HIPAA authorization may be either included in the informed consent or obtained&#xD;
        separately.&#xD;
&#xD;
          -  Males 18 years of age and above&#xD;
&#xD;
          -  Body weight &gt; 30kg&#xD;
&#xD;
          -  History of radical prostatectomy&#xD;
&#xD;
          -  Histologically confirmed prostate cancer with progressive disease defined as:&#xD;
&#xD;
          -  Rising PSA (50% or more increase to a level of 0.50 ng/mL or more, based on at least 3&#xD;
             PSA determinations obtained at least 1 week apart). The 50% rise in PSA is across the&#xD;
             3 determinations, and these determinations do not need to be sequential.&#xD;
&#xD;
          -  PSA doubling time of &lt;/= 9 months as calculated according to the Memorial Sloan&#xD;
             Kettering Cancer Center nomogram&#xD;
&#xD;
          -  No evidence of metastatic disease on conventional imaging (CT/MRI and bone scan).&#xD;
             However, subjects with pelvic and/or retroperitoneal nodes &lt; 2cm in the short axis&#xD;
             will be permitted on study, as they are considered not to have definitive metastases.&#xD;
             (Note: Metastatic disease on investigational imaging, Prostate Specific Membrane&#xD;
             Antigen-targeted (PSMA) PET, PET-choline, or other novel PET tracers who do not have&#xD;
             evidence of metastatic disease using conventional imaging (CT/MRI, bone scan) are&#xD;
             allowed.)&#xD;
&#xD;
          -  Molecular evidence of DDR deleterious mutations (somatic or germline), including&#xD;
             BRCA1, BRCA2, ATM, CHEK2, FANCA, RAD51C, RAD51D, PALB2, BRIP1, BARD1, or CDK12.&#xD;
             Mutations may be truncating, splice site mutations, missense or homozygous deletions.&#xD;
             Mutation status is determined by a local laboratory with the result documented in the&#xD;
             subject's medical record, previously obtained genomic testing from a CLIA-certified&#xD;
             lab, or via archival or fresh tissue.&#xD;
&#xD;
          -  ECOG status of ≤1&#xD;
&#xD;
          -  Normal organ function with acceptable initial laboratory values within 14 days of&#xD;
             treatment start:&#xD;
&#xD;
          -  WBC ≥ 2000/ul&#xD;
&#xD;
          -  ANC ≥ 1500/uL&#xD;
&#xD;
          -  Hemoglobin ≥ 10g/dL&#xD;
&#xD;
          -  Platelet count ≥100,000/ul&#xD;
&#xD;
          -  Creatinine Clearance ≥ 51 mL/min estimated using the Cockcroft-Gault equation&#xD;
&#xD;
          -  Bilirubin ≤ 1.5 ULN (unless documented Gilbert's disease)&#xD;
&#xD;
          -  SGOT (AST) ≤ 2.5 x ULN (unless liver metastases are present, in which case AST must be&#xD;
             5 x ULN)&#xD;
&#xD;
          -  SGPT (ALT) ≤ 2.5 x ULN (unless liver metastases are present, in which case ALT must be&#xD;
             5 x ULN)&#xD;
&#xD;
          -  Non-castrate level of testosterone defined as a value ≥ 150 ng/dL&#xD;
&#xD;
          -  Life expectancy of ≥ 52 weeks.&#xD;
&#xD;
          -  Agree to use two medically acceptable, highly effective forms of birth control (e.g.,&#xD;
             spermicide in conjunction with a barrier such as a condom) or sexual abstinence for&#xD;
             the duration of the study, including 180 days after the last dose of study drug. Sperm&#xD;
             donation is prohibited during the study and for 3 months after the last dose of study&#xD;
             drug. Female partners of child bearing potential should use hormonal or barrier&#xD;
             contraception unless postmenopausal or abstinent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No other malignancy from which the subject has been disease-free for less than 3&#xD;
             years, with the exception of adequately treated and cured non-invasive malignancies&#xD;
             such as basal or squamous cell skin cancer or superficial bladder cancer.&#xD;
&#xD;
          -  Less than one month prior to treatment start from last prior regimen or radiation&#xD;
             exposure. Prior radiotherapy to the prostate (adjuvant or salvage radiotherapy) is&#xD;
             allowed.&#xD;
&#xD;
          -  No prior investigational use with an anti-PD(1) including durvalumab or anti-CTLA4&#xD;
             antibody.&#xD;
&#xD;
          -  No prior treatment with a PARP inhibitor, including olaparib.&#xD;
&#xD;
          -  No concomitant or prior therapy with any of the following: IL-2, interferon, or other&#xD;
             non-study immunotherapy regimens; immunosuppressive agents; or chronic use of systemic&#xD;
             corticosteroids within 6 weeks of treatment start. Exceptions include:&#xD;
&#xD;
        intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular&#xD;
        injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day&#xD;
        ofprednisone or its equivalent; Steroids as premedication for hypersensitivity reactions&#xD;
        (e.g., CT scan premedication)&#xD;
&#xD;
          -  No receipt of live attenuated vaccine within 30 days prior to treatment start Note:&#xD;
             enrolled subjects should not receive live vaccine while receiving IP and up to 30 days&#xD;
             after the last dose of study therapy&#xD;
&#xD;
          -  Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin,&#xD;
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,&#xD;
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.&#xD;
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout&#xD;
             period prior to treatment start is 2 weeks.&#xD;
&#xD;
          -  Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin,&#xD;
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or&#xD;
             moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout&#xD;
             period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3&#xD;
             weeks for other agents.&#xD;
&#xD;
          -  More than 2 cycles of intermittent hormones for the treatment of biochemical&#xD;
             recurrence, with a cycle defined as a period of consistent ADT (generally 3-12 months)&#xD;
             followed by intentional cessation of ADT without re-initiation of ADT until the PSA&#xD;
             rises. Prior ADT in the treatment of localized prostate cancer or with salvage&#xD;
             radiation therapy is allowed. Prior use of abiraterone acetate with prednisone,&#xD;
             enzalutamide, apalutamide, or other androgen receptor/androgen biosynthesis inhibitors&#xD;
             are allowed if used in the localized or biochemically recurrent disease state provided&#xD;
             that there was no evidence of disease progression while on these therapies.&#xD;
&#xD;
          -  No medical conditions such as uncontrolled hypertension, uncontrolled diabetes&#xD;
             mellitus, cardiac disease that would, in the opinion of the investigator, make this&#xD;
             protocol unreasonably hazardous.&#xD;
&#xD;
          -  Subjects considered a poor medical risk due to a serious, uncontrolled medical&#xD;
             disorder or non-malignant systemic disease. Examples include, but are not limited to,&#xD;
             uncontrolled ventricular arrhythmia, myocardial infarction within 3 months of&#xD;
             treatment start, uncontrolled major seizure disorder, unstable spinal cord&#xD;
             compression, superior vena cava syndrome, extensive interstitial bilateral lung&#xD;
             disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder&#xD;
             that prohibits obtaining informed consent.&#xD;
&#xD;
          -  No active infection including tuberculosis (TB) (clinical evaluation that includes&#xD;
             clinical history, physical examination and radiographic findings, and TB testing in&#xD;
             line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg)&#xD;
             result), hepatitis C, or active infection with human immunodeficiency virus (positive&#xD;
             HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as&#xD;
             presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.&#xD;
             Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain&#xD;
             reaction is negative for HCV RNA&#xD;
&#xD;
          -  No autoimmune disease: subjects with a history of inflammatory bowel disease,&#xD;
             including ulcerative colitis and Crohn's Disease, are excluded from this study, as are&#xD;
             subjects with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic&#xD;
             progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune&#xD;
             vasculitis *e.g., Sarcoidosis syndrome or Wegener's granulomatosis with&#xD;
             polyangiitis+); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre&#xD;
             syndrome and myasthenia gravis); Graves' disease. Exceptions include history of&#xD;
             eczema, vitiligo, alopecia, hypothyroidism (e.g., following Hashimoto syndrome) , and&#xD;
             any chronic skin condition that does not require systemic therapy; subjects without&#xD;
             active disease in the last 5 years prior to treatment start may be included but only&#xD;
             after consultation with the treating physician. Exceptions may be made on a case by&#xD;
             case basis upon discussion with the Sponsor Principal Investigator.&#xD;
&#xD;
          -  No history of active primary immunodeficiency&#xD;
&#xD;
          -  No major surgery within 4 weeks of treatment start. Subjects must have recovered from&#xD;
             any significant effects of any major surgery but investigators may discuss with the&#xD;
             Sponsor Principal Investigator in the case of any exceptions.&#xD;
&#xD;
          -  No blood transfusion within 28 days of treatment start.&#xD;
&#xD;
          -  Resting ECG with QTc &gt; 470 msec on 2 or more time points within a 24 hour period or&#xD;
             family history of long QT syndrome&#xD;
&#xD;
          -  Enrollment in another clinical trial with a therapeutic agent. Subjects may co-enroll&#xD;
             on investigational imaging studies (e.g., PSMA PET) or correlative trials.&#xD;
&#xD;
          -  No previous allogeneic bone marrow transplant or double umbilical cord blood&#xD;
             transplant.&#xD;
&#xD;
          -  No history of leptomeningeal carcinomatosis&#xD;
&#xD;
          -  No unresolved toxicity (Common Terminology Criteria for Adverse Event (CTCAE) Grade&#xD;
             &gt;/= 2) caused by previous anticancer therapy, excluding alopecia, vitiligo, and the&#xD;
             laboratory values described in the inclusion criteria. Subjects with Grade &gt;/= 2&#xD;
             neuropathy will be evaluated on a case-by-case basis after consultation with the&#xD;
             Sponsor Principal Investigator. Subjects with irreversible toxicity not reasonably&#xD;
             expected to be exacerbated by treatment with study drugs may be included only after&#xD;
             consultation with the Sponsor Principal Investigator&#xD;
&#xD;
          -  No subjects who are HIV-positive on combination antiretroviral therapy because of the&#xD;
             potential for pharmacokinetic interactions with olaparib. In addition, these subjects&#xD;
             are at increased risk of lethal infections when treated with marrow suppressive&#xD;
             therapy.&#xD;
&#xD;
          -  No subjects with baseline moderate to severe hepatic impairment (Child-Pugh Class B&#xD;
             and C).&#xD;
&#xD;
          -  No subjects with myelodysplastic syndrome/acute myeloid leukemia or with features&#xD;
             suggestive of MDS/AML.&#xD;
&#xD;
          -  No known allergy to any of the compounds under investigation or excipients of the&#xD;
             product.&#xD;
&#xD;
          -  Subjects unable to swallow orally administered medication and subjects with&#xD;
             gastrointestinal disorders likely to interfere with absorption of the study&#xD;
             medication.&#xD;
&#xD;
          -  No other condition which, in the opinion of the investigator, would preclude&#xD;
             participation in this trial.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karen Autio, MD, MsC</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Basking Ridge</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Commack</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>July 7, 2023</last_update_submitted>
  <last_update_submitted_qc>July 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>radical prostatectomy</keyword>
  <keyword>Olaparib</keyword>
  <keyword>Durvalumab</keyword>
  <keyword>Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer</keyword>
  <keyword>18-480</keyword>
  <keyword>Memorial Sloan Kettering Cancer Center</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic 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>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
  </patient_data>
  <!-- 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/NCT03810105
org study id: 18-480
nct id: NCT03810105
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine if the combination of olaparib and durvalumab are
      better than the standard of care for treating prostate cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Therapeutic efficacy as defined by number of participants with an undetectable PSA
time frame: 1 year
description: To assess the therapeutic efficacy as defined by an undetectable PSA (<0.05 or PSA <0.10 for institutions where this is the lower limit of detection) with non-castrate levels of testosterone using the combination olaparib (PARP inhibition) with durvalumab (PDL1 inhibition) at 24 months (cycle 24) in biochemically recurrent prostate cancer
arm group label: Castration Sensitive Biochemically Recurrent Prostate Cancer
arm group type: Experimental
description: Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer
intervention type: Drug
intervention name: Olaparib
description: Olaparib 300mg twice daily (600mg total daily dose)
arm group label: Castration Sensitive Biochemically Recurrent Prostate Cancer
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab 1500mg IV monthly
arm group label: Castration Sensitive Biochemically Recurrent Prostate Cancer
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Karen Autio, MD, MsC
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Durvalumab
mesh term: Olaparib
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)