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Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency

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ClinicalTrials.gov Identifier: NCT03442556
Recruitment Status : Recruiting
First Posted : February 22, 2018
Last Update Posted : March 5, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Brief Summary:
This phase II trial studies how well docetaxel, carboplatin, and rucaparib camsylate work in treating patients with castration resistant prostate cancer with homologous recombination deoxyribonucleic acid (DNA) repair deficiency that has spread to other places in the body. Drugs used in chemotherapy, such as docetaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rucaparib camsylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving induction docetaxel and carboplatin followed by maintenance rucaparib camsylate may work better in treating patients with castration resistant prostate cancer.

Condition or disease Intervention/treatment Phase
ATM Gene Mutation BRCA1 Gene Mutation BRCA2 Gene Mutation Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Homologous Recombination Deficiency Prostate Carcinoma Metastatic in the Bone PSA Level Greater Than or Equal to Two PSA Progression Stage IV Prostate Adenocarcinoma AJCC v7 Drug: Carboplatin Drug: Docetaxel Other: Laboratory Biomarker Analysis Drug: Rucaparib Camsylate Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine radiographic progression free survival with 4 cycles of docetaxel with carboplatin followed by maintenance rucaparib camsylate (rucaparib) in the treatment of patients with metastatic castration resistant prostate cancer with homologous recombination DNA repair deficiency.

SECONDARY OBJECTIVES:

I. To assess maximal prostate-specific antigen (PSA) response to induction docetaxel and carboplatin.

II. To assess PSA response to switch maintenance with rucaparib. III. To assess PSA response duration to docetaxel and carboplatin followed by switch maintenance with rucaparib.

IV. To assess response of measurable disease.

OUTLINE:

INDUCTION: Patients receive docetaxel intravenously (IV) and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive rucaparib camsylate orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 24, 2018
Estimated Primary Completion Date : May 15, 2024
Estimated Study Completion Date : May 15, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive rucaparib camsylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

Drug: Docetaxel
Given IV
Other Names:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Rucaparib Camsylate
Given PO
Other Names:
  • 8-Fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic Acid Salt
  • C0-338
  • Rubraca
  • Rucaparib Phosphate




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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)

  3. 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)

  4. 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 ]
  5. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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, so long as prior therapy does not include platinum chemotherapy or a PARP inhibitor
  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03442556


Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Heather H. Cheng    206-606-1406    hhcheng@uw.edu   
Principal Investigator: Heather H. Cheng         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Heather Cheng Fred Hutch/University of Washington Cancer Consortium

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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT03442556     History of Changes
Other Study ID Numbers: 9841
NCI-2018-00016 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9841 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
RG1717043 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: February 22, 2018    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Carcinoma
Prostatic Neoplasms
Adenocarcinoma
DNA Repair-Deficiency Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Metabolic Diseases
Carboplatin
Docetaxel
Rucaparib
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors