TriangleNCT02952534 · CITED IN SOURCE DOCUMENTS
A Study of Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2023-06-09
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR)
Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV)
Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR)
Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator
Confirmed PSA Response (≥ 50% Decrease) by Gene as Assessed by Local Laboratory
Confirmed PSA Response (≥ 90% Decrease) by Gene as Assessed by Local Laboratory
Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR)
Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator
Overall Survival (OS) by Gene
Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR)
Clinical Benefit Rate (CBR) by Gene Per Investigator
Time to PSA Progression by Gene
Steady State Trough (Cmin) Level Rucaparib Concentrations
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- MALE
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Oral rucaparib (monotherapy)
- intervention Names
- Drug: Rucaparib
- label
- Rucaparib
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Rucaparib
- description
- Rucaparib will be administered daily
- name
- Rucaparib
- other Names
- CO-338
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 277
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- 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.
- secondary Outcomes
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- Steady State Trough (Cmin) Level Rucaparib Concentrations
- time Frame
- Participants were assessed at Study Day 29, Day 57, Day 85 and Day 113
Full study description
- 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.
Source references
- references
- citation
- Abida W, Campbell D, Patnaik A, Bryce AH, Shapiro J, Bambury RM, Zhang J, Burke JM, Castellano D, Font A, Ganju V, Hardy-Bessard AC, McDermott R, Sautois B, Spaeth D, Voog E, Piulats JM, Pintus E, Ryan CJ, Merseburger AS, Daugaard G, Heidenreich A, Fizazi K, Loehr A, Despain D, Simmons AD, Dowson M, Go J, Watkins SP, Chowdhury S. Rucaparib for the Treatment of Metastatic Castration-resistant Prostate Cancer Associated with a DNA Damage Repair Gene Alteration: Final Results from the Phase 2 TRITON2 Study. Eur Urol. 2023 Sep;84(3):321-330. doi: 10.1016/j.eururo.2023.05.021. Epub 2023 Jun 3.
- pmid
- 37277275
- type
- DERIVED
- citation
- Collins K, Cheng L. Reprint of: morphologic spectrum of treatment-related changes in prostate tissue and prostate cancer: an updated review. Hum Pathol. 2023 Mar;133:92-101. doi: 10.1016/j.humpath.2023.02.007. Epub 2023 Mar 8.
- pmid
- 36898948
- type
- DERIVED
- citation
- Green ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
- pmid
- 35397664
- type
- DERIVED
- citation
- Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.
- pmid
- 32203306
- type
- DERIVED
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Preserved source evidence · Not medical advice