E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic Urothelial Carcinoma |
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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 | LLT |
E.1.2 | Classification code | 10064467 |
E.1.2 | Term | Urothelial carcinoma |
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 | PT |
E.1.2 | Classification code | 10044412 |
E.1.2 | Term | Transitional cell carcinoma |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective for this study is:
• To evaluate objective response rate (ORR) in molecularly-defined homologous recombination deficiency (HRD)-positive and intent-to-treat (ITT) populations using a prospectively defined molecular signature. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives for this study are:
• To evaluate duration of response (DOR)
• To estimate progression-free survival (PFS)
• To estimate overall survival (OS)
• To evaluate safety and tolerability of rucaparib
• To evaluate steady-state pharmacokinetics (PK) of rucaparib |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Have histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
• Received 1 or 2 prior standard of care regimens for advanced or metastatic disease
• Confirmed radiologic disease progression during or following recent treatment
• Mandatory biopsy is required during screening
• Measurable disease per RECIST v1.1
• Adequate organ function
• ECOG 0 or 1 |
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E.4 | Principal exclusion criteria |
• Prior treatment with a PARP inhibitor
• Symptomatic and/or untreated CNS metastases
• Duodenal stent and/or any gastrointestinal disorder that may interfere with absorption of rucaparib |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint of ORR is defined as a best confirmed response of CR or PR by RECIST v1.1 as assessed by the investigator. The ORR will be summarized with frequencies and percentages for the ITT and HRD-positive populations as well as other HRD subgroups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Tumor assessments will be performed during screening (baseline), at the end of every 8 calendar weeks (±7 days) relative to the first dose of rucaparib (Cycle 1 Day 1) up to 18 months, then every 12 calendar weeks (±7 days), until confirmed radiologic disease progression by RECIST v1.1 criteria, as assessed by the investigator. |
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E.5.2 | Secondary end point(s) |
Efficacy:
Duration of Response (DOR):
Duration of confirmed response is defined as the time from the date that a response is first reported to the time that progression is first documented after the confirmed response.
Progression-free Survival (PFS):
PFS will be calculated as 1+ the number of days from the first dose of rucaparib to disease progression or death due to any cause, whichever occurs first.
Patients without a documented event of progression will be censored on the date of their last adequate tumor assessment (ie, radiologic assessment) or date of first dose of rucaparib if no post-baseline tumor assessments have been performed.
Overall Survival (OS):
Overall survival (OS) is defined as the date from first dose of rucaparib to the date of death due to any cause. Patients who have not died will be censored at the date last known to be alive.
Safety:
Safety endpoints include incidence of AEs, clinical laboratory abnormalities, and dose modifications.
Data from all patients in the safety population will be included in the safety analyses. AEs, clinical laboratory results, vital signs, ECG results, ECOG performance status, body weight, and concomitant medications/ procedures will be tabulated and summarized.
PK:
The PK data and selected safety and efficacy endpoints will be included in exploratory population PK and exposure-response analyses, and the results will be reported separately. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
DOR, PFS, OS please refer to E.5.2
Safety;
The investigator has the responsibility for assessing the safety of the patients and for compliance with the protocol to ensure study integrity. During the screening period, unless otherwise required by local regulations, SAEs which are related to protocol-mandated assessments will be reported. Once enrolled and rucaparib is administered, patients will be monitored for all AEs/SAEs/AESIs during study participation and until 28 days after the last dose of rucaparib. After the 28-day window, only treatment-related SAEs and all AESIs, irrespective of causality, need to be reported.
PK:
Plasma samples are to be collected for trough level PK analysis of rucaparib 1 hour before the morning dose on Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1 |
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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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 |
France |
Germany |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |