A Study of Olaparib and Durvalumab in Prostate Cancer

NCT03810105 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 18-480
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 8

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.

Conditions

Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  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

  1 year

Study Arms (1)

Castration Sensitive Biochemically Recurrent Prostate Cancer

EXPERIMENTAL

Castration Sensitive Biochemically Recurrent Non-Metastatic Prostate Cancer

Drug: Olaparib; Drug: Durvalumab

Interventions

Olaparib DRUG

Olaparib 300mg twice daily (600mg total daily dose)

Castration Sensitive Biochemically Recurrent Prostate Cancer

Durvalumab DRUG

Durvalumab 1500mg IV monthly

Castration Sensitive Biochemically Recurrent Prostate Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (8)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60637, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

olaparib; durvalumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Karen Autio, MD
• Organization: Memorial Sloan Kettering Cancer Center

autiok@mskcc.org

646-422-4632

Study Officials

• Karen Autio, MD, MsC

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2019
• First Posted: January 18, 2019
• Study Start: March 7, 2019
• Primary Completion: July 6, 2023
• Study Completion: July 6, 2023
• Last Updated: April 9, 2024
• Results First Posted: April 9, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF

Locations

US (8)