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ATM Gene MutationPhase 2NCT03442556

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

A Phase 2 study testing Carboplatin, Docetaxel and Laboratory Biomarker Analysis in people with ATM Gene Mutation and BRCA1 Gene Mutation, run by University of Washington at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Carboplatin, Docetaxel and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
24 Aug 2018to 4 Jun 2025
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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)

Who cannot join

  • 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)
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Carboplatin, Docetaxel, Laboratory Biomarker Analysis, Rucaparib Camsylate, Rucaparib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • DocetaxelDrug

    Also called Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Rucaparib CamsylateDrug

    Also called 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

    Given PO

  • RucaparibDrug

    Also called 283173-50-2, 6H-Pyrrolo(4,3,2-ef)(2)benzazepin-6-one, 8-Fluoro-1,3,4,5-tetrahydro-2-(4-((methylamino)methyl)phenyl)-

    Given PO

Study groups in NCT03442556
Study groupRoleWhat they receive
Treatment (docetaxel, carboplatin, rucaparib camsylate)ExperimentalINDUCTION: 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.
Receives: Drug: Carboplatin; Drug: Docetaxel; Other: Laboratory Biomarker Analysis; Drug: Rucaparib Camsylate; Drug: Rucaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Radiologic progression free survival (rPFS) is defined as the time 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. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by investigator assessment using the RECIST 1.1/PCWG3 criteria.

    Measured: 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 3.75 years.

Secondary outcomes (5)

  1. Overall Response Rate (ORR) of Measurable Disease (PCWG3) (Complete Response or Partial Response) Assessed by Modified RECIST Version 1.1 Criteria

    Overall response rate of measurable disease (PCWG3): radiologic ORR (CR or PR per modified RECIST Version 1.1 criteria and no bone progression per PCWG3 prior to a CR or PR) by investigator assessment in patients with measurable visceral and/or nodal disease at baseline per IRR (Cohort A). An analysis of radiologic ORR by the investigator will also be conducted as supportive to the primary endpoint.

    Measured: Up to 3.75 years

  2. Prostate-specific Antigen (PSA) Nadir After Induction

    Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90). Number of patients achieving a PSA decline from baseline of ≥50% (PSA50) or ≥90% (PSA90). The change in PSA was calculated relative to the PSA level at the start of cycle 1.

    Measured: Up to 13 weeks

  3. PSA Nadir After Maintenance

    Rate of confirmed PSA decrease from baseline, assessed by a local laboratory (PSA50 and PSA90) using postchemotherapy PSA as the baseline. The most recent PSA level before PARPi initiation was used as the baseline PSA. Number of patients achieving a PSA decline from baseline of ≥50% (PSA50) or ≥90% (PSA90).

    Measured: Up to 3.5 years

  4. PSA Response Duration

    PSA-response duration: duration of confirmed response is defined as the time from the date that a response (PSA decrease ≥ 50%) is first reported to the time that PSA progression is first documented.

    Measured: From the date that a response (PSA decrease >= 50%) is first reported to the time that PSA progression is first documented, assessed up to 3.75 years

  5. Time to PSA Progression (PCWG3)

    Time to PSA progression is defined as the time 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. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.

    Measured: 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 3.75 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2018
  2. Study start24 Aug 2018
  3. Primary completion4 Jun 2025
  4. Study completion4 Jun 2025

Why it stopped: Terminated due to insufficient funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03442556
Sponsor's protocol ID
9841
Other IDs
NCI-2018-00016, 9841, RG1717043
Status last verified
Aug 2026
First submitted
9 Feb 2018
Last updated
26 Aug 2026
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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