- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03442556
Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency
PLATI-PARP: A Phase 2 Study of Induction Docetaxel and Carboplatin Followed by Maintenance Rucaparib in Treatment of Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency
Study Overview
Status
Conditions
- BRCA1 Gene Mutation
- BRCA2 Gene Mutation
- Castration-Resistant Prostate Carcinoma
- Homologous Recombination Deficiency
- PSA Progression
- Stage IV Prostate Adenocarcinoma AJCC v7
- Castration Levels of Testosterone
- ATM Gene Mutation
- Prostate Carcinoma Metastatic in the Bone
- PSA Level Greater Than or Equal to Two
Intervention / Treatment
Detailed Description
OUTLINE:
INDUCTION: Patients receive docetaxel intravenously (IV) and carboplatin IV on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive rucaparib camsylate orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Heather H. Cheng
- Phone Number: 206-606-1406
- Email: hhcheng@uw.edu
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Signed informed consent form (ICF) providing agreement to adhere to the dosing schedule, report for all trial visits and authorization, use and release of health and research trial information
- Histologically or cytologically confirmed adenocarcinoma of the prostate (excluding predominant small cell histology)
- Ongoing gonadal androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogues, antagonists or orchiectomy; patients who have not had an orchiectomy must be maintained on effective GnRH analogue/antagonist therapy
- Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart
Presence of metastatic disease on bone or computed tomography (CT) scan
- Evaluable disease progression by modified RECIST 1.1 (Response Evaluation Criteria in Solid Tumors)
- Bone disease on bone scan
- Prior therapy with sipuleucel-T, abiraterone, enzalutamide, docetaxel, and/or cabazitaxel; there is no limit to the number of prior treatment regimens in the castration resistant setting, so long as prior therapy does not include platinum chemotherapy or a PARP inhibitor; prior platinum chemotherapy in the hormone sensitive setting is permitted, so long as it has been at least 6 months since last dose
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
- Life expectancy >= 12 weeks
No prior malignancy is allowed except:
- Adequately treated basal cell or squamous cell skin cancer or
- In situ carcinoma of any site or
- Other adequately treated malignancy for which the patient has been disease-free for at least one year (any prior chemotherapy is allowed)
Documented evidence of at least ONE or MORE of the following:
* Pathogenic mutation or inactivating alteration of a gene involved in homologous recombination repair in the tumor
Note, that if this alteration is identified in a circulating tumor deoxyribonucleic acid (ctDNA) assay, the variant-allele fraction must be > 20% to indicate relevance to predominant tumor clone
- Mutation in one or more other genes involved in homologous DNA recombination repair in the tumor may be included at investigator's discretion
- Homologous recombination repair deficiency by genomic signature in the tumor by BROCA-HR, Foundation One or equivalent assay
- Presence of pathogenic or likely pathogenic germline mutation/variant in BRCA2, BRCA1, ATM or PALB2
- Note: Germline mutations in other HR genes will be considered at investigator's discretion)
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 14 days of first dose of study drug)
- Platelets > 100 x 10^9/L (within 14 days of first dose of study drug)
- Hemoglobin >= 9 g/dL (within 14 days of first dose of study drug)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN; if liver metastases, then =< 5 x ULN (within 14 days of first dose of study drug)
- Bilirubin =< 1.5 x ULN (< 2 x ULN if hyperbilirubinemia is due to Gilbert's syndrome) (within 14 days of first dose of study drug)
- Serum creatinine =< 1.5 x ULN or estimated glomerular filtration rate (GFR) >= 45 mL/min using the Cockcroft Gault formula (within 14 days of first dose of study drug)
Exclusion Criteria:
- Currently receiving active therapy for other neoplastic disorders
- Symptomatic and/or untreated central nervous system (CNS) metastases; patients with asymptomatic previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, active or symptomatic viral hepatitis or chronic liver disease
- Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class II-IV heart disease or cardiac ejection fraction measurement of < 35 % at baseline
- Treatment with an investigational therapeutic drug within 30 days of cycle 1
- Prior therapy with a PARP inhibitor (e.g., olaparib, talazoparib, veliparib, niraparib, rucaparib)
- Prior therapy with a platinum chemotherapy (e.g. cisplatin, carboplatin, oxaliplatin) in the castration resistant setting; (prior platinum chemotherapy in the hormone sensitive setting is permitted, so long as time since last dose is 6 months or greater)
- Active, ongoing toxicity (Common Terminology Criteria for Adverse Events [CTCAE] grade 2 or higher) from prior therapy
- Presence of dementia, psychiatric illness, and/or social situations limiting compliance with study requirements or understanding and/or giving of informed consent
- Pre-existing duodenal stent and/ or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
- Any condition(s), medical or otherwise, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained
Study Plan
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 (docetaxel, carboplatin, rucaparib camsylate)
INDUCTION: Patients receive docetaxel IV and carboplatin IV on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive rucaparib camsylate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Correlative studies
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Radiographic progression free survival assessed by assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1/Prostate Cancer Working Group 3 (PCWG3) criteria
Time Frame: From first dose of docetaxel/carboplatin to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, assessed up to 6 years
|
From first dose of docetaxel/carboplatin to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, assessed up to 6 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR) of measurable disease (PCWG3) (complete response or partial response) assessed by modified RECIST version 1.1 criteria
Time Frame: Up to 6 years
|
Up to 6 years
|
|
Prostate-specific antigen (PSA) nadir after induction
Time Frame: Up to 6 years
|
Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90)
|
Up to 6 years
|
PSA nadir after maintenance
Time Frame: Up to 6 years
|
Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90)
|
Up to 6 years
|
PSA response duration
Time Frame: From the date that a response (PSA decrease >= 50%) is first reported to the time that PSA progression is first documented, assessed up to 6 years
|
From the date that a response (PSA decrease >= 50%) is first reported to the time that PSA progression is first documented, assessed up to 6 years
|
|
Time to PSA progression (PCWG3)
Time Frame: From first dose of docetaxel/carboplatin to the date that a >= 25% increase and absolute increase of >= 2 ng/mL above the nadir (or baseline value for patients who did not have a decline in PSA) in PSA was measured, assessed up to 6 years
|
The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.
|
From first dose of docetaxel/carboplatin to the date that a >= 25% increase and absolute increase of >= 2 ng/mL above the nadir (or baseline value for patients who did not have a decline in PSA) in PSA was measured, assessed up to 6 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Heather H. Cheng, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Carcinoma
- DNA Repair-Deficiency Disorders
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Poly(ADP-ribose) Polymerase Inhibitors
- Docetaxel
- Carboplatin
- Rucaparib
Other Study ID Numbers
- 9841 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
- NCI-2018-00016 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- RG1717043 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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