Olaparib in Prostate Cancer Patients With Evidence of Homologous Recombination Deficiency as Assessed Using an Integrated Genomic Signature

University of Washington1 site in 1 country2 target enrollmentNovember 9, 2022

ConditionsCastration-Resistant Prostate Carcinoma Prostate Adenocarcinoma

InterventionsOlaparib

DrugsOlaparib

Overview

Phase: Phase 2
Intervention: Olaparib
Conditions: Castration-Resistant Prostate Carcinoma
Sponsor: University of Washington
Enrollment: 2
Locations: 1
Primary Endpoint: Lowest On-treatment Prostate Specific Antigen (PSA)
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This phase II trial investigates the effect of olaparib in treating patients with castration resistant prostate adenocarcinoma. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

OUTLINE: Patients receive olaparib orally (PO) twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up to 1 year.

Registry

clinicaltrials.gov

Start Date

November 9, 2022

End Date

October 15, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

Male

Investigators

Sponsor

University of Washington

Responsible Party

Principal Investigator

Michael Schweizer

Associate Professor

University of Washington

Eligibility Criteria

Inclusion Criteria

•Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
•Subject must be \>= 18 years of age at the time of signing the informed consent form
•Individuals who have documented histologically confirmed adenocarcinoma of the prostate
•Subject must have evidence of castration resistant prostate cancer as evidenced by PSA progression (per Prostate Cancer Working Group 3 \[PCWG3\] criteria) and a castrate serum testosterone level (i.e. =\< 50 mg/dL)
•PSA must be at least 2 ng/mL and rising on two successive measurements at least two weeks apart
•At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computed tomography (CT) scan, magnetic resonance imaging (MRI), or positron emission tomography (PET) and is suitable for repeated assessment
•Must have progressed on abiraterone and/or a second-generation androgen receptor (AR) antagonist (i.e. enzalutamide, apalutamide, or darolutamide). If these were given in the hormone sensitive setting, patients must also have progressed on at least one prior approved therapy for CRPC
•Must have archival tissue available or be willing to undergo metastatic biopsy in order to perform next-generation deoxyribonucleic acid (DNA) sequencing and undergo whole exome sequencing
•Patient must have a positive LOH score on prior University of Washington (UW) OncoPlex testing
•Hemoglobin \>= 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days prior to administration of study treatment)

Exclusion Criteria

•As judged by the investigator, any evidence of serious and/or unstable pre-existing medical or psychiatric condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial
•Other malignancy unless curatively treated with no evidence of disease for \>= 5 years except: adequately treated non-melanoma skin cancer and non-muscle invasive bladder cancer
•Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fridericia's formula \[QTcF\] prolongation \> 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
•Persistent toxicities (\> Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia
•Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
•Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
•Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, 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
•Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
•Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are not receiving active treatment or have a detectable viral load
•Patients with known active hepatitis (i.e. hepatitis B or C).

Arms & Interventions

Treatment (Olaparib)

Patients receive olaparib orally (PO) twice daily (BID). Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Intervention: Olaparib

Outcomes

Primary Outcomes

Lowest On-treatment Prostate Specific Antigen (PSA)

Time Frame: At least 12 weeks of olaparib treatment

The proportion of patients achieving at least a 50% decline in PSA from baseline will be presented.

Secondary Outcomes

Overall Response Rate (ORR)(Up to 12.3 weeks)
Radiographic Progression Free Survival (PFS)(Up to 12.3 weeks)
Prostate Specific Antigen (PSA) Progression Free Survival (PFS)(Up to 16.6 weeks)
Overall Survival(Up to 12.3 weeks)