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

Memorial Sloan Kettering Cancer Center8 sites in 1 country5 target enrollmentMarch 7, 2019

ConditionsProstate Cancer

InterventionsOlaparib Durvalumab

DrugsOlaparib Durvalumab

Overview

Phase: Phase 2
Intervention: Olaparib
Conditions: Prostate Cancer
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 5
Locations: 8
Primary Endpoint: Therapeutic Efficacy as Defined by Number of Participants With an Undetectable PSA
Status: Terminated
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

March 7, 2019

End Date

July 6, 2023

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Male

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

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 0.50 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 \</= 9 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, BRIP1, BARD1, or CDK

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. Prior use of abiraterone acetate with prednisone, enzalutamide, apalutamide, or other androgen receptor/androgen biosynthesis inhibitors are allowed if used in the localized or biochemically recurrent disease state provided that there was no evidence of disease progression while on these therapies.

Arms & Interventions

Castration Sensitive Biochemically Recurrent Prostate Cancer

Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer

Intervention: Olaparib

Castration Sensitive Biochemically Recurrent Prostate Cancer

Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer

Intervention: Durvalumab

Outcomes

Primary Outcomes

Therapeutic Efficacy as Defined by Number of Participants With an Undetectable PSA

Time Frame: 1 year

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