A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (TRITON3)
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| ClinicalTrials.gov Identifier: NCT02975934 |
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Recruitment Status :
Active, not recruiting
First Posted : November 29, 2016
Results First Posted : August 16, 2023
Last Update Posted : March 20, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Castration Resistant Prostate Cancer | Drug: Rucaparib Drug: Abiraterone acetate or Enzalutamide or Docetaxel | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 405 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | TRITON3: A Multicenter, Randomized, Open Label Phase 3 Study of Rucaparib Versus Physician's Choice of Therapy for Patients With Metastatic Castration Resistant Prostate Cancer Associated With Homologous Recombination Deficiency |
| Actual Study Start Date : | June 13, 2017 |
| Actual Primary Completion Date : | August 25, 2022 |
| Estimated Study Completion Date : | December 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Rucaparib
Oral rucaparib (monotherapy).
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Drug: Rucaparib
Rucaparib will be administered daily.
Other Name: CO-338 |
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Active Comparator: Abiraterone acetate or Enzalutamide or Docetaxel
Oral abiraterone acetate (monotherapy, given in combination with prednisone). Oral enzalutamide (monotherapy). Intravenous docetaxel (monotherapy, given in combination with prednisone or prednisolone).
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Drug: Abiraterone acetate or Enzalutamide or Docetaxel
Abiraterone acetate and enzalutamide will be administered daily. Docetaxel will be administered every 3 weeks.
Other Name: Zytiga (abiraterone acetate) or Xtandi (enzalutamide) or Taxotere (docetaxel) |
- Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration [ Time Frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) ]
The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).
Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).
- Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined [ Time Frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) ]
The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).
Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria (Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).
- Interim Overall Survival in Participants With a BRCA Alteration [ Time Frame: From enrollment to primary completion of study (up to approximately 5 years) ]Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participant was last known to be alive.
- Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined [ Time Frame: From enrollment to primary completion of study (up to approximately 5 years) ]Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participants was last known to be alive.
- Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration [ Time Frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) ]
ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).
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.
- Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined [ Time Frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) ]
ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).
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.
- Duration of Response (DOR) by IRR in Participants With a BRCA Alteration [ Time Frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) ]DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented.
- Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined [ Time Frame: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years) ]DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented.
- PSA Response in Participants With a BRCA Alteration [ Time Frame: From enrollment to primary completion of study (up to approximately 5 years) ]Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory.
- PSA Response in Participants With a BRCA or ATM Alteration Combined [ Time Frame: From enrollment to primary completion of study (up to approximately 5 years) ]Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory.
- Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration [ Time Frame: From enrollment to 6 months ]Defined as the percentage of participants with a complete response (CR), partial response (PR), and stable disease (SD) according to modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria.
- Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined [ Time Frame: From enrollment to 6 months ]Defined as the percentage of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD), according to Modified RECIST Version 1.1 with no progression in bone per PCWG3 Criteria.
- Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration [ Time Frame: From enrollment to primary completion of study (up to approximately 5 years) ]Time to PSA progression is defined as the time from randomization to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for participants 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.
- Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined [ Time Frame: From enrollment to primary completion of study (up to approximately 5 years) ]Time to PSA progression is defined as the time from randomization to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for participants 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.
- Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P [ Time Frame: From enrollment to up to approximately 25 weeks ]Changes in health and pain status from baseline to week 25 using: Functional Assessment of Cancer Therapy-Prostate questionnaire (FACT-P total score, on a scale of 0 to 156 where a higher score is better quality of life). The greater the decrease in score (ie more negative) from baseline to week 25 the greater the decrease in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.
- Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF [ Time Frame: From enrollment to up to approximately 25 weeks ]Changes in health and pain status from baseline to week 25 using: Brief Pain Inventory-Short Form (BPI-SF) questionnaire (on a scale of 1 to 10, from mild to severe, for pain and pain-interference scores). A decrease indicates less severe pain/interference. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.
- Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L [ Time Frame: From enrollment to up to approximately 25 weeks ]Changes in health and pain status from baseline to week 25 using: EuroQol-5D-5L Visual Analogue Scale (EQ-5D-5L VAS; on a scale from 100 to 0, from best to worst health status). The greater the increase in score (including more negative) from baseline to week 25 the greater the increase in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase.
- Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling [ Time Frame: From enrollment to week 5 of dosing ]Mean trough PK plasma concentration over time in the safety population with at least one PK sample collected at timepoints week 5, 9, 13 and 17; only Week 5 data presented.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Be 18 years old at the time the informed consent is signed
- Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate that is metastatic
- Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM)
- Be eligible for treatment with physician's choice of comparator treatment (abiraterone acetate, enzalutamide or docetaxel)
- Experienced disease progression after having received 1 prior next generation androgen receptor-targeted therapy
- Have a deleterious mutation in a BRCA1/2 or ATM gene
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
- Prior treatment with chemotherapy for metastatic castration-resistant prostate cancer
- 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 study drug
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): NCT02975934
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Documents provided by pharmaand GmbH:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | pharmaand GmbH |
| ClinicalTrials.gov Identifier: | NCT02975934 |
| Other Study ID Numbers: |
CO-338-063 |
| First Posted: | November 29, 2016 Key Record Dates |
| Results First Posted: | August 16, 2023 |
| Last Update Posted: | March 20, 2024 |
| Last Verified: | March 2024 |
| 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 zr pharma& Austria GmbH |
| 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@pharmaand.com. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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CRPC PARP inhibitor PARPi BRCA ATM HRD TRITON |
homologous recombination DNA repair DNA defect DNA anomaly germline somatic mCRPC |
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Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Genital Diseases Urogenital Diseases Prostatic Diseases Male Urogenital Diseases Docetaxel Abiraterone Acetate Rucaparib |
Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Steroid Synthesis Inhibitors Enzyme Inhibitors Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Cytochrome P-450 Enzyme Inhibitors Poly(ADP-ribose) Polymerase Inhibitors |