E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic castration-resistant prostate cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076506 |
E.1.2 | Term | Castration-resistant prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of rucaparib based on the response rate in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination deficiency (HRD) who progressed on AR-targeted therapy (abiraterone acetate, enzalutamide, apalutamide or investigational AR-targeted agent) and taxane-based chemotherapy in the castration resistant setting |
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E.2.2 | Secondary objectives of the trial |
• To assess duration of response (DOR) • To assess radiologic PFS (rPFS) • To assess overall survival (OS) • To assess clinical benefit rate (CBR) • To assess PSA response ≥ 50% (all patients) • To assess PSA response ≥ 90% (all patients) • To assess time to PSA progression • To characterize the steady-state pharmacokinetics (PK) of rucaparib in mCRPC patients • To assess safety and tolerability |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Be 18 years old at the time the informed consent form is signed 2. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate 3. Be surgically or medically castrated, with serum testosterone levels of ≤ 50 ng/dL (1.73 nM) 4. 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 5. Have a deleterious mutation in BRCA1/2 or ATM (Cohorts A and B), or molecular evidence of other homologous recombination deficiency (Cohort C)
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E.4 | Principal exclusion criteria |
1. Active second malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer 2. Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide or any platinum-based chemotherapy 3. Symptomatic and/or untreated central nervous system metastases 4. Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of rucaparib |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints: for Cohort A: The primary endpoint is ORR as assessed by central IRR and analyzed both overall and separately for patients with deleterious BRCA1/2 and ATM mutations. ORR for Cohort A is defined as the proportion of patients with a confirmed response of CR or PR using modified RECIST Version 1.1 (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).
for Cohort B: The primary endpoint is PSA response (≥ 50% decrease) as assessed by a local laboratory and analyzed both overall and separately for patients with deleterious BRCA1/2 and ATM mutations. The proportion of patients with ≥ 50% PSA decrease from baseline will be reported.
For Cohort C: The primary endpoint is ORR defined as the proportion of patients with a confirmed response of CR or PR using either modified RECIST Version 1.1 (if measurable visceral and/or nodal disease is present) or ≥ 50% PSA decrease from baseline (if visceral and/or nodal disease is absent). For patients with measurable disease, response will be assessed by central IRR. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor assessments by CT/MRI and bone scans will be performed during screening, at the end of every 8 calendar weeks (± 7 days) from Study Day 1 (Week 1) up to 24 weeks and every 12 calendar weeks (± 7 days) thereafter, and at the Treatment Discontinuation Visit, if applicable. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints: - Duration of response is defined as the time from the date that a response (modified RECIST Version 1.1 or PSA ≥ 50%) is first reported to the time that progression (using modified RECIST Version 1.1/PCWG3 criteria or PSA-progression criteria, respectively) is documented. - Radiologic PFS (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. Radiologic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by independent central radiological review using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease. - OS is defined as the date from first dose of rucaparib to the date of death due to any cause. - CBR is defined as the combination of CR, PR, and SD as defined by modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria. Per RECIST, to be assigned a best overall response of CR or PR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. - Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline to lowest post-baseline PSA result, with a consecutive assessment conducted at least 3 weeks later. PSA response will be calculated for all patients with PSA values at baseline and at least 1 post-baseline assessment. PSA will be assessed by a local laboratory. - 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 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.
Safety Analyses Adverse events (AEs), clinical laboratory results, vital signs, ECOG performance status, body weight, and concomitant medications/ procedures will be tabulated and summarized. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tumor assessments by CT/MRI and bone scans will be performed during screening, at the end of every 8 calendar weeks (± 7 days) from Study Day 1 (Week 1) up to 24 weeks and every 12 calendar weeks (± 7 days) thereafter, and at the Treatment Discontinuation Visit, if applicable.
PSA will be measured at Day 1, and then every 28 days and at the treatment Discontinuation Visit.
OS will be monitored until patient death
Safety will be monitored at all visits |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 77 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Canada |
Denmark |
France |
Germany |
Ireland |
Israel |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |