Clinical Trials /

A Study of Olaparib and Durvalumab in Prostate Cancer

NCT03810105

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Olaparib and Durvalumab in Prostate Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 18-480
  • NCT ID: NCT03810105

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
OlaparibCastration Sensitive Biochemically Recurrent Prostate Cancer
DurvalumabCastration Sensitive Biochemically Recurrent Prostate Cancer

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Castration Sensitive Biochemically Recurrent Prostate CancerExperimentalCastration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer
  • Olaparib
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent and HIPAA authorization for the
             release of personal health information. A signed informed consent must be obtained
             before screening procedures are performed.

        NOTE: HIPAA authorization may be either included in the informed consent or obtained
        separately.

          -  Males 18 years of age and above

          -  Body weight > 30kg

          -  History of radical prostatectomy

          -  Histologically confirmed prostate cancer with progressive disease defined as:

          -  Rising PSA (50% or more increase to a level of 1 ng/mL or more, based on at least 3
             PSA determinations obtained at least 1 week apart). The 50% rise in PSA is across the
             3 determinations, and these determinations do not need to be sequential.

          -  PSA doubling time of </= 8 months as calculated according to the Memorial Sloan
             Kettering Cancer Center nomogram

          -  No evidence of metastatic disease on conventional imaging (CT/MRI and bone scan).
             However, subjects with pelvic and/or retroperitoneal nodes < 2cm in the short axis
             will be permitted on study, as they are considered not to have definitive metastases.
             (Note: Metastatic disease on investigational imaging, Prostate Specific Membrane
             Antigen-targeted (PSMA) PET, PET-choline, or other novel PET tracers who do not have
             evidence of metastatic disease using conventional imaging (CT/MRI, bone scan) are
             allowed.)

          -  Molecular evidence of DDR deleterious mutations (somatic or germline), including
             BRCA1, BRCA2, ATM, CHEK2, FANCA, RAD51C, RAD51D, PALB2, or CDK12. Mutations may be
             truncating, splice site mutations, missense or homozygous deletions. Mutation status
             is determined by a local laboratory with the result documented in the subject's
             medical record, previously obtained genomic testing from a CLIA-certified lab, or via
             archival or fresh tissue.

          -  ECOG status of </= 1

          -  Normal organ function with acceptable initial laboratory values within 14 days of
             treatment start:

        WBC ≥ 2000/ul ANC ≥ 1500/uL Hemoglobin ≥ 10g/dL Platelet count ≥100,000/ul Creatinine
        Clearance ≥ 51 mL/min estimated using the Cockcroft-Gault equation Bilirubin ≤ 1.5 ULN
        (unless documented Gilbert's disease) SGOT (AST) ≤ 2.5 x ULN (unless liver metastases are
        present, in which case AST must be 5 x ULN) SGPT (ALT) ≤ 2.5 x ULN (unless liver metastases
        are present, in which case ALT must be 5 x ULN) Non-castrate level of testosterone defined
        as a value 150 ng/dL

          -  Life expectancy of >/= 52 weeks.

          -  Agree to use two medically acceptable, highly effective forms of birth control (e.g.,
             spermicide in conjunction with a barrier such as a condom) or sexual abstinence for
             the duration of the study, including 180 days after the last dose of study drug. Sperm
             donation is prohibited during the study and for 3 months after the last dose of study
             drug. Female partners of child bearing potential should use hormonal or barrier
             contraception unless postmenopausal or abstinent.

        Exclusion Criteria:

          -  No other malignancy from which the subject has been disease-free for less than 3
             years, with the exception of adequately treated and cured non-invasive malignancies
             such as basal or squamous cell skin cancer or superficial bladder cancer.

          -  Less than one month prior to treatment start from last prior regimen or radiation
             exposure. Prior radiotherapy to the prostate (adjuvant or salvage radiotherapy) is
             allowed.

          -  No prior investigational use with an anti-PD(1) including durvalumab or anti-CTLA4
             antibody.

          -  No prior treatment with a PARP inhibitor, including olaparib.

          -  No concomitant or prior therapy with any of the following: IL-2, interferon, or other
             non-study immunotherapy regimens; immunosuppressive agents; or chronic use of systemic
             corticosteroids within 6 weeks of treatment start. Exceptions include:

        intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular
        injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day
        ofprednisone or its equivalent; Steroids as premedication for hypersensitivity reactions
        (e.g., CT scan premedication)

          -  No receipt of live attenuated vaccine within 30 days prior to treatment start Note:
             enrolled subjects should not receive live vaccine while receiving IP and up to 30 days
             after the last dose of study therapy

          -  Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin,
             clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
             saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.
             ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
             period prior to treatment start is 2 weeks.

          -  Concomitant use of known strong (e.g., phenobarbital, enzalutamide, phenytoin,
             rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or
             moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout
             period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
             weeks for other agents.

          -  More than 2 cycles of intermittent hormones for the treatment of biochemical
             recurrence, with a cycle defined as a period of consistent ADT (generally 3-12 months)
             followed by intentional cessation of ADT without re-initiation of ADT until the PSA
             rises. Prior ADT in the treatment of localized prostate cancer or with salvage
             radiation therapy is allowed.

          -  No medical conditions such as uncontrolled hypertension, uncontrolled diabetes
             mellitus, cardiac disease that would, in the opinion of the investigator, make this
             protocol unreasonably hazardous.

          -  Subjects considered a poor medical risk due to a serious, uncontrolled medical
             disorder or non-malignant systemic disease. Examples include, but are not limited to,
             uncontrolled ventricular arrhythmia, myocardial infarction within 3 months of
             treatment start, uncontrolled major seizure disorder, unstable spinal cord
             compression, superior vena cava syndrome, extensive interstitial bilateral lung
             disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder
             that prohibits obtaining informed consent.

          -  No active infection including tuberculosis (TB) (clinical evaluation that includes
             clinical history, physical examination and radiographic findings, and TB testing in
             line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg)
             result), hepatitis C, or active infection with human immunodeficiency virus (positive
             HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as
             presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible.
             Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
             reaction is negative for HCV RNA

          -  No autoimmune disease: subjects with a history of inflammatory bowel disease,
             including ulcerative colitis and Crohn's Disease, are excluded from this study, as are
             subjects with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic
             progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
             vasculitis *e.g., Sarcoidosis syndrome or Wegener's granulomatosis with
             polyangiitis+); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre
             syndrome and myasthenia gravis); Graves' disease. Exceptions include history of
             eczema, vitiligo, alopecia, hypothyroidism (e.g., following Hashimoto syndrome) , and
             any chronic skin condition that does not require systemic therapy; subjects without
             active disease in the last 5 years prior to treatment start may be included but only
             after consultation with the treating physician. Exceptions may be made on a case by
             case basis upon discussion with the Sponsor Principal Investigator.

          -  No history of active primary immunodeficiency

          -  No major surgery within 4 weeks of treatment start. Subjects must have recovered from
             any significant effects of any major surgery but investigators may discuss with the
             Sponsor Principal Investigator in the case of any exceptions.

          -  No blood transfusion within 28 days of treatment start.

          -  Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or
             family history of long QT syndrome

          -  Enrollment in another clinical trial with a therapeutic agent. Subjects may co-enroll
             on investigational imaging studies (e.g., PSMA PET) or correlative trials.

          -  No previous allogeneic bone marrow transplant or double umbilical cord blood
             transplant.

          -  No history of leptomeningeal carcinomatosis

          -  No unresolved toxicity (Common Terminology Criteria for Adverse Event (CTCAE) Grade
             >/= 2) caused by previous anticancer therapy, excluding alopecia, vitiligo, and the
             laboratory values described in the inclusion criteria. Subjects with Grade >/= 2
             neuropathy will be evaluated on a case-by-case basis after consultation with the
             Sponsor Principal Investigator. Subjects with irreversible toxicity not reasonably
             expected to be exacerbated by treatment with study drugs may be included only after
             consultation with the Sponsor Principal Investigator

          -  No subjects who are HIV-positive on combination antiretroviral therapy because of the
             potential for pharmacokinetic interactions with olaparib. In addition, these subjects
             are at increased risk of lethal infections when treated with marrow suppressive
             therapy.

          -  No subjects with baseline moderate to severe hepatic impairment (Child-Pugh Class B
             and C).

          -  No subjects with myelodysplastic syndrome/acute myeloid leukemia or with features
             suggestive of MDS/AML.

          -  No known allergy to any of the compounds under investigation or excipients of the
             product.

          -  Subjects unable to swallow orally administered medication and subjects with
             gastrointestinal disorders likely to interfere with absorption of the study
             medication.

          -  No other condition which, in the opinion of the investigator, would preclude
             participation in this trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Therapeutic efficacy as defined by an undetectable PSA
Time Frame:1 year
Safety Issue:
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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • radical prostatectomy
  • Olaparib
  • Durvalumab
  • Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer
  • 18-480
  • Memorial Sloan Kettering Cancer Center

Last Updated