Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Study Overview
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Brief Summary
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The purpose of the ATLAS study is to determine how patients with locally advanced unresectable or metastatic urothelial carcinoma respond to treatment with rucaparib.

Official Title
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A Phase 2, Open-label Study of Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Conditions
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Bladder Cancer, Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Renal Pelvis Carcinoma, Ureter Carcinoma, Urinary Bladder Carcinoma, Urethra Carcinoma, Muscle Invasive Bladder Cancer

Intervention / Treatment
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* Drug: Rucaparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histologically or cytologically confirmed locally advanced unresectable or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra) Received 1 or 2 prior treatment 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rucaparib<br>Oral rucaparib (monotherapy) | Drug: Rucaparib<br>* Rucaparib will be administered daily.<br>* Other names: CO-338;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Per RECIST Version 1.1 | ORR is defined as the proportion of patients with a confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR), is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. | Time from first dose to date of progression, up to approximately 19 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator | PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. | Cycle 1 Day 1 to End of Treatment, up to approximately 10 months | 
| Overall Survival | Overall survival (OS) was defined as time from the date of first dose of rucaparib to the date of death due to any cause. Patients without a known date of death were to be censored on the date the patient was last known to be alive. A Kaplan-Meier analysis of OS was planned, however, due to early study termination and limited duration of OS follow-up, a descriptive summary of total deaths are presented. This includes deaths recorded on study (from first dose of study drug until 28 days after last dose of study drug), and deaths recorded in long-term follow-up (from last dose +28 days until death, loss to follow-up, withdrawal of consent, or study closure). | The total study time for reporting of deaths was approximately 19 months. | 
| Pharmacokinetics - Trough (Cmin) Level Rucaparib Concentrations | Plasma were 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. | From Cycle 2 Day 1 to Cycle 4 Day 1, or approximately 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HRD, PARP inhibitor, PARPi, ATLAS, homologous recombination, DNA repair, LOH, DNA defect, DNA anomaly, Rucaparib, MIBC