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

  • STATUS
    Recruiting
  • End date
    May 15, 2025
  • participants needed
    20
  • sponsor
    University of Washington
Updated on 12 May 2022
ct scan
gonadotropin
cancer
absolute neutrophil count
androgens
gilbert's syndrome
glomerular filtration rate
testosterone
metastasis
neutrophil count
carboplatin
tumor cells
biomarker analysis
docetaxel
antiandrogen therapy
androgen suppression
bone scan
abiraterone
bone disease
orchiectomy
enzalutamide
serum testosterone
androgen
adenocarcinoma
parp inhibitor
lhrh analogue
palb2
adenocarcinoma of the prostate
sipuleucel-t
adenocarcinoma of prostate

Summary

This phase II trial studies how well docetaxel with carboplatin followed by rucaparib camsylate works in treating patients with metastatic castration resistant prostate cancer (spread outside of prostate and resistant to testosterone suppression) with homologous recombination DNA repair deficiency. Chemotherapy drugs, such as docetaxel and carboplatin, work to stop the growth of cancer cells, by stopping them from dividing or spreading. Rucaparib camsylate may stop the growth of tumor cells with defects in the ability to repair mistakes in DNA by forcing additional errors so that the cancer cells cannot overcome the number of errors and will then die. Giving induction docetaxel and carboplatin followed by maintenance rucaparib camsylate may work better in treating patients with castration resistant prostate cancer.

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 time to PSA progression with induction docetaxel and carboplatin followed by maintenance with rucaparib.

V. 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 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.

Details
Condition 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
Treatment laboratory biomarker analysis, docetaxel, carboplatin, rucaparib, Rucaparib Camsylate
Clinical Study IdentifierNCT03442556
SponsorUniversity of Washington
Last Modified on12 May 2022

Eligibility

Yes No Not Sure

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
Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
Life expectancy >= 12 weeks
the castration resistant setting, so long as prior therapy does not include
No prior malignancy is allowed except
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
Adequately treated basal cell or squamous cell skin cancer or
In situ carcinoma of any site or
months since last dose
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
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)
Note: Germline mutations in other HR genes will be considered at investigator's
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)
discretion)
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)
Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (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
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