- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04951492
Olaparib for the Treatment of Castration Resistant Prostate Adenocarcinoma
December 7, 2023 updated by: University of Washington
Olaparib in Prostate Cancer Patients With Evidence of Homologous Recombination Deficiency as Assessed Using an Integrated Genomic Signature
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.
Study Overview
Status
Terminated
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
2
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Michael Schweizer
- Phone Number: 206.606.6252
- Email: schweize@uw.edu
Study Locations
-
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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)
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to administration of study treatment)
- Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study treatment)
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =< 5 x ULN (within 28 days prior to administration of study treatment)
- Patients must have creatinine clearance estimated of >= 51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test (within 28 days prior to administration of study treatment)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients must have an estimated life expectancy >= 16 weeks
- Male patients must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential
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).
- Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA)
- Any previous treatment with PARP inhibitor, including olaparib
- Any previous treatment with platinum chemotherapy in the metastatic castration-resistant setting
- Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
- Concomitant use of known strong CYP3A inhibitors (eg. 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 starting olaparib 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
- Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product
- Involvement in the planning and/or conduct of the study
- Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (Olaparib)
Patients receive olaparib orally (PO) twice daily (BID).
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Lowest on-treatment prostate specific antigen (PSA)
Time Frame: At least 12 weeks of olaparib treatment
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Will be calculated along with 90% confidence intervals (CI) using Wilson's method.
PSA changes will be presented as waterfall plots per Prostate Cancer Working Group 3 criteria recommendations.
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At least 12 weeks of olaparib treatment
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Overall response rate (ORR)
Time Frame: Up to 1 year
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Will be defined as a 30% decrease from baseline per Response Evaluation Criteria in Solid Tumors 1.1 criteria at any time point.
The percent of patients with ORR and 90% CI, calculated using Wilson's method, will be provided.
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Up to 1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Radiographic response rate
Time Frame: Up to 1 year
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Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1 criteria.
Radiographic responses will be presented as waterfall plots.
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Up to 1 year
|
Radiographic progression free survival (PFS)
Time Frame: Up to 1 year
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Will be estimated using the Kaplan-Meier method.
Median times to event will be reported with 90% CIs using linear interpolation between steps of the survival curve.
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Up to 1 year
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PSA PFS
Time Frame: Up to 1 year
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Will be assessed by Prostate Cancer Working Group 3 criteria.
Will be estimated using the Kaplan-Meier method.
Median times to event will be reported with 90% CIs using linear interpolation between steps of the survival curve.
|
Up to 1 year
|
Overall survival
Time Frame: Up to 1 year
|
Will be estimated using the Kaplan-Meier method.
Median times to event will be reported with 90% CIs using linear interpolation between steps of the survival curve.
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Up to 1 year
|
Incidence and severity of adverse events
Time Frame: Up to 1 year
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Will be assessed according to the National Cancer Institute- Common Terminology Criteria for Adverse Events version 4.0.
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Up to 1 year
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Michael Schweizer, Fred Hutch/University of Washington Cancer Consortium
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 9, 2022
Primary Completion (Actual)
October 15, 2023
Study Completion (Actual)
October 15, 2023
Study Registration Dates
First Submitted
June 28, 2021
First Submitted That Met QC Criteria
June 28, 2021
First Posted (Actual)
July 6, 2021
Study Record Updates
Last Update Posted (Estimated)
December 14, 2023
Last Update Submitted That Met QC Criteria
December 7, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Adenocarcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Olaparib
- Poly(ADP-ribose) Polymerase Inhibitors
Other Study ID Numbers
- RG1121519 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
- NCI-2021-06147 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 10759 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Castration-Resistant Prostate Carcinoma
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Universität des SaarlandesRecruitingProstate Cancer Metastatic | Advanced Prostate Carcinoma | Castration Resistant Prostatic CancerGermany
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Vadim S KoshkinEli Lilly and Company; Prostate Cancer FoundationActive, not recruitingCastration-Resistant Prostate Carcinoma | Stage IV Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8 | Stage IVB Prostate Cancer AJCC v8 | Metastatic Castration-resistant Prostate Cancer | Metastatic Prostate Adenocarcinoma | Metastatic Castration-resistant Prostate CarcinomaUnited States
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Nuvation Bio Inc.WithdrawnProstate Cancer | Prostate Neoplasm | Cancer of the Prostate | Prostatic Cancer | Castrate Resistant Prostate Cancer | Cancer of Prostate | Castration Resistant Prostatic Cancer | Castration Resistant Prostatic NeoplasmsUnited States
-
Janux TherapeuticsRecruitingProstate Cancer | Metastatic Castration-resistant Prostate Cancer | Castration Resistant Prostatic CancerUnited States, Australia
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Cancer Immunotherapy Trials NetworkCompletedCastration-Resistant Prostate Carcinoma | Metastatic Prostate Carcinoma | Stage IV Prostate Cancer | Castration Levels of TestosteroneUnited States
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Myovant Sciences GmbHRecruitingMetastatic Castration-Resistant Prostate Cancer | Metastatic Castration-Sensitive Prostate Cancer | Non-Metastatic Castration-Resistant Prostate CancerUnited States
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Astellas Pharma IncPfizerCompletedCastration-resistant Prostate CancerJapan
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Dana-Farber Cancer InstituteProgenics Pharmaceuticals, Inc.Not yet recruitingProstate Cancer | Metastatic Castration-resistant Prostate Cancer | Metastatic Castration-resistant Prostate CarcinomaUnited States
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Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)UnknownCastration-Resistant Prostate Carcinoma | Metastatic Prostate Carcinoma | Stage IVB Prostate Cancer AJCC v8 | Castration Levels of Testosterone | Prostate Carcinoma Metastatic in the BoneUnited States
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University of WashingtonNational Cancer Institute (NCI)CompletedCastration-Resistant Prostate Carcinoma | Metastatic Prostate Carcinoma | Recurrent Prostate Carcinoma | Castration Levels of Testosterone | Stage IV Prostate AdenocarcinomaUnited States
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Memorial Sloan Kettering Cancer CenterActive, not recruitingSmall Cell Lung Carcinoma | Small-cell Lung CancerUnited States
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AstraZenecaMerck Sharp & Dohme LLC; Iqvia Pty LtdCompletedMalignant Solid TumorBelgium
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CSPC Ouyi Pharmaceutical Co., Ltd.CompletedHealthy ParticipantsChina
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Dana-Farber Cancer InstituteNovartis; AstraZenecaCompleted
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AstraZenecaEuropean Network of Gynaecological Oncological Trial Groups (ENGOT)CompletedEpithelial Ovarian CancerDenmark, France, Germany, Italy, Spain, Poland, Belgium, Canada, United Kingdom, Israel, Norway
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AstraZenecaMerck Sharp & Dohme LLC; European Network of Gynaecological Oncological Trial... and other collaboratorsActive, not recruitingRelapsed Ovarian Cancer | Following Complete or Partial Response to Platinum Based Chemotherapy | Platinum Sensitive | BRCA MutatedKorea, Republic of, France, China, Italy, United States, Israel, United Kingdom, Canada, Japan, Germany, Brazil, Netherlands, Belgium, Poland, Australia, Russian Federation, Spain
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Nordic Society of Gynaecological Oncology - Clinical...Hellenic Cooperative Oncology Group; European Network of Gynaecological Oncological... and other collaboratorsRecruiting
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Qilu Pharmaceutical Co., Ltd.Completed
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SandozCompleted
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Leiden University Medical CenterUniversity Medical Center Groningen; Erasmus Medical CenterRecruitingBRCA1 Mutation | BRCA2 Mutation | Homologous Recombination Deficiency | Ovarian Neoplasm EpithelialNetherlands