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A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (TRITON2)

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ClinicalTrials.gov Identifier: NCT02952534
Recruitment Status : Completed
First Posted : November 2, 2016
Results First Posted : June 8, 2022
Last Update Posted : July 6, 2022
Sponsor:
Collaborator:
Foundation Medicine
Information provided by (Responsible Party):
Clovis Oncology, Inc.

Study Description
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Brief Summary:
The purpose of this study is to determine how patients with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib.

Condition or disease Intervention/treatment Phase
Metastatic Castration Resistant Prostate Cancer Drug: Rucaparib Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 277 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: TRITON2: A Multicenter, Open-label Phase 2 Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer Associated With Homologous Recombination Deficiency
Actual Study Start Date : February 15, 2017
Actual Primary Completion Date : July 18, 2021
Actual Study Completion Date : July 27, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Rucaparib

Arms and Interventions
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Arm Intervention/treatment
Experimental: Rucaparib
Oral rucaparib (monotherapy)
 Drug: Rucaparib
Rucaparib will be administered daily
Other Name: CO-338


Outcome Measures
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Primary Outcome Measures :
  1. Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR) [ Time Frame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years. ]
    The primary efficacy endpoint is confirmed radiographic ORR by central IRR. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.


Secondary Outcome Measures :
  1. Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV) [ Time Frame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years. ]
    A supportive efficacy endpoint is confirmed radiographic ORR by INV. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

  2. Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR) [ Time Frame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years. ]
    A secondary efficacy endpoint is DOR by central IRR. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.

  3. Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator [ Time Frame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years. ]
    A secondary efficacy endpoint is DOR as assessed by the investigator. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.

  4. Confirmed PSA Response (≥ 50% Decrease) by Gene as Assessed by Local Laboratory [ Time Frame: PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months. ]
    A secondary endpoint is confirmed PSA (prostate-specific antigen) response (≥ 50% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 50% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir in PSA.

  5. Confirmed PSA Response (≥ 90% Decrease) by Gene as Assessed by Local Laboratory [ Time Frame: PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months. ]
    A secondary endpoint is confirmed PSA (prostate-specific antigen) response (≥ 90% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 90% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir in PSA.

  6. Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR) [ Time Frame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years. ]
    A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by IRR. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by IRR using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.

  7. Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator [ Time Frame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years. ]
    A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by Investigator. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.

  8. Overall Survival (OS) by Gene [ Time Frame: From date of first dose until event, loss to follow-up, withdrawal of consent, or study closure: an overall median of approximately 33.1 months ]
    A secondary efficacy endpoint is Overall Survival (OS). OS is defined as the date from first dose of rucaparib to the date of death due to any cause, +1 day.

  9. Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR) [ Time Frame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years. ]
    A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by IRR. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.

  10. Clinical Benefit Rate (CBR) by Gene Per Investigator [ Time Frame: Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years. ]
    A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by Investigator. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.

  11. Time to PSA Progression by Gene [ Time Frame: PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months. ]
    A secondary efficacy endpoint is time to PSA progession. Time to PSA progression is defined as the time from first dose of rucaparib to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline if there was no PSA decline after baseline) in PSA was measured, plus 1 day. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later (unless the PSA progression occurred at the last recorded PSA assessment). If confirmed, the date used for time of PSA progression is the earlier of the 2 PSA dates.

  12. Steady State Trough (Cmin) Level Rucaparib Concentrations [ Time Frame: Participants were assessed at Study Day 29, Day 57, Day 85 and Day 113 ]
    Trough (Cmin) concentrations of rucaparib are summarized for all patients with at least one PK sample collected. The absolute values of rucaparib plasma concentration at each time point are presented by gene.


Eligibility Criteria
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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:

  • Be 18 years old at the time the informed consent form is signed
  • Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate
  • Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
  • Experienced disease progression after having received at least 1 but no more than 2 prior next-generation androgen receptor-targeted therapies, and 1 prior taxane-based chemotherapy, for castration-resistant disease
  • Have a deleterious mutation in BRCA1/2 or ATM, or molecular evidence of other homologous recombination deficiency

Exclusion Criteria:

  • Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer
  • Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide or any platinum-based chemotherapy
  • Symptomatic and/or untreated central nervous system metastases
  • Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of rucaparib
Contacts and Locations
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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): NCT02952534


Locations
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Sponsors and Collaborators
Clovis Oncology, Inc.
Foundation Medicine
  Study Documents (Full-Text)

Documents provided by Clovis Oncology, Inc.:
Study Protocol  [PDF] August 24, 2020
Statistical Analysis Plan  [PDF] July 2, 2019

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02952534    
Other Study ID Numbers: CO-338-052
First Posted: November 2, 2016    Key Record Dates
Results First Posted: June 8, 2022
Last Update Posted: July 6, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by Clovis Oncology.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data will be made available to qualified researchers after the primary, secondary, and/or exploratory outcomes of the study are reported or published and for 1 year thereafter.
Access Criteria: Requests for de-identified datasets will be made available to qualified researchers following submission of a methodologically sound proposal to medinfo@clovisoncology.com.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Clovis Oncology, Inc.:
CRPC
PARP inhibitor
PARPi
BRCA
ATM
HRD
TRITON
homologous recombination
DNA repair
DNA defect
DNA anomaly
BARD1
BRIP1
 CDK12
CHEK2
FANCA
NBN
PALB2
RAD51
RAD51B
RAD51C
RAD51D
RAD54L
germline
somatic
mCRPC
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
 Rucaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents