Rucaparib Hepatic Impairment Study in Patients With a Solid Tumor

NCT03521037 | Completed Phase 1 FDA Drug

• 1 other identifier: CO-338-078
• Study Type: interventional
• Target: 16
• Locations: 3 countries
• Sites: 6

Brief Summary

Phase 1, open-label, parallel group, PK, safety and tolerability study in patients with an advanced solid tumor and either normal hepatic function (Group 1, n = 8) or moderate hepatic impairment (Group 2, n = 8) according to the NCI-ODWG criteria. Patients in Group 1 and Group 2 may be enrolled in parallel, with preferential enrollment of Group 2 patients before Group 1 patients. The study will consist of 2 parts: a single-dose PK part (Part I) and a continuous rucaparib treatment part (Part II).

Conditions

Neoplasms

Keywords

rucaparib; CO-338; Clovis; Clovis Oncology; PARP inhibitor; hepatic impairment

Outcome Measures

Primary Outcomes (2)

• Maximum plasma rucaparib concentration (Cmax)

  PK parameter of rucaparib to be calculated from the plasma concentration-time data

  day 1 to day 7

• Area under the plasma rucaparib concentration-time curve from time zero up to the last time point with quantifiable concentration (AUC0-last)

  PK parameter of rucaparib to be calculated from the plasma concentration-time data

  day 1 to day 7

Secondary Outcomes (12)

• Area under the plasma rucaparib concentration-time curve from time zero up to time infinity (AUC0-inf)

  day 1 to day 7

• Terminal half-life (t1/2) of rucaparib

  day 1 to day 7

• Time to attain maximum plasma rucaparib concentration (Tmax)

  day 1 to day 7

• Apparent clearance (CL/F) of rucaparib

  day 1 to day 7

• Apparent volume of distribution during terminal phase (Vz/F) of rucaparib

  day 1 to day 7

Other Outcomes (8)

• Maximum plasma metabolite concentration (Cmax)

  day 1 to day 7

• Area under the plasma metabolite concentration-time curve from time zero up to the last time point with quantifiable concentrations (AUC0-last)

  day 1 to day 7

• Area under the plasma metabolite concentration-time curve from time zero up to time infinity (AUC0-inf)

  day 1 to day 7

Study Arms (1)

no name

EXPERIMENTAL

Group 1: patients with normal hepatic function Group 2: patients who have moderate hepatic impairment

Drug: Rucaparib camsylate

Interventions

Rucaparib camsylate DRUG

In Part I, eligible patients will receive a single oral dose of 600 mg rucaparib followed by intensive plasma PK sampling up to Day 7 (hour 144). In Part II, patients may continue to receive continuous oral rucaparib in 28 day cycles.

Also known as: rubraca

no name

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Patients:
• Patients ≥18 years of age at the time the ICF is signed;
• Patients with a histologically or cytologically confirmed advanced solid tumor who, in the opinion of the Investigator, could potentially benefit from treatment with rucaparib
• ECOG PS less than or equal to 2
• Adequate bone marrow and renal function
• Hepatically Impaired Patients (in addition):
• Stable hepatic impairment as judged by the Investigator
• Moderate Hepatic Impairment (NCI-ODWG criteria) during Screening
• Patients with Normal Hepatic Function (in addition):
• Normal Hepatic Function (NCI-ODWG criteria)

You may not qualify if:

• All Patients:
• Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or investigational drugs within 14 days prior to day 1
• Ongoing toxicity ≥ Grade 2 per Common Terminology Criteria for Adverse Events criteria (CTCAE version 4.03)
• Prior treatment with any poly adenosine diphosphate ribose polymerase inhibitor
• Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, stenting or poorly controlled hypertension within the last 3 months prior to Screening
• Pre-existing duodenal stent, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
• Hospitalization for bowel obstruction within 3 months prior to Day 1
• Untreated or symptomatic central nervous system (CNS) metastases
• Evidence or history of bleeding disorder
• Acute illness within 14 days prior to Day 1
• Active second malignancy
• Hepatically Impaired Patients (in addition):
• Severe hepatic encephalopathy (Grade \>2);
• History of liver transplantation;
• Advanced ascites or ascites that require drainage and albumin supplementation, as judged by the Investigator;

Sponsors & Collaborators

• pharmaand GmbH: lead

Study Sites (6)

Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej

Biała Podlaska, 21-500, Poland

Location

Med Polonia Sp. z o.o.

Poznan, 60-693, Poland

Location

Zachodniopomorskie Centrum Onkologii w Szczecinie

Szczecin, 71-730, Poland

Location

BioVirtus Centrum Medyczne

Warsaw, 02-681, Poland

Location

Summit Clinical Research s.r.o.

Bratislava, 831 01, Slovakia

Location

Northern Centre for Cancer Care

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

rucaparib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: May 11, 2018
• Study Start: February 27, 2018
• Primary Completion: September 27, 2019
• Study Completion: February 24, 2021
• Last Updated: June 9, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1); GB (1); PL (4)