Locally Advanced or Metastatic Urothelial Carcinoma MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10044412 Term: Transitional cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Rucaparib 200 mg
Product Code: CO-338
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Rucaparib
CAS Number: 283173-50-2
Current Sponsor code: CO-338
Other descriptive name:
Sponsors
Clovis Oncology, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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;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. ;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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;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 | — |
Countries
France, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactChief Medical Officer
Clovis Oncology UK Ltd
Outcome results
None listed