Clinical Trials /

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

NCT03442556

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 9841
  • SECONDARY ID: NCI-2018-00016
  • SECONDARY ID: 9841
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT03442556

Conditions

  • 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

Interventions

DrugSynonymsArms
CarboplatinBlastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, RibocarboTreatment (docetaxel, carboplatin, rucaparib camsylate)
DocetaxelDocecad, RP56976, Taxotere, Taxotere Injection ConcentrateTreatment (docetaxel, carboplatin, rucaparib camsylate)
Rucaparib Camsylate8-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 PhosphateTreatment (docetaxel, carboplatin, rucaparib camsylate)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (docetaxel, carboplatin, rucaparib camsylate)ExperimentalINDUCTION: 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.
  • Carboplatin
  • Docetaxel
  • Rucaparib Camsylate

Eligibility 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:

               -  Biallelic inactivation of genes involved in homologous recombination repair in
                  the tumor

               -  Biallelic inactivation of 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

               -  Clearly pathogenic or likely pathogenic germline mutation in BRCA2, BRCA1 and/or
                  ATM

               -  (Note: the following are not alone sufficient for eligibility and require
                  additional criteria to be met: germline variant of uncertain significance in
                  BRCA1, BRCA2 and/or ATM; germline mutations in other HR genes)

          -  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: 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

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:Prostate-specific antigen (PSA) nadir after induction
Time Frame:Up to 6 years
Safety Issue:
Description:Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90)
Measure:PSA nadir after maintenance
Time Frame:Up to 6 years
Safety Issue:
Description:Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90)
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Washington

Last Updated

February 20, 2018