Back to resultsRucaparib Hepatic Impairment Study in Patients With a Solid Tumor
Primary Purpose
Neoplasms
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Rucaparib camsylate
Sponsored by
About this trial
This is an interventional other trial for Neoplasms focused on measuring rucaparib, CO-338, Clovis, Clovis Oncology, PARP inhibitor, hepatic impairment
Eligibility Criteria
Inclusion Criteria:
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)
Exclusion Criteria:
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;
- Acute damage of the liver with Grade 4 AST/ALT values
Sites / Locations
- Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
- Med Polonia Sp. z o.o.
- Zachodniopomorskie Centrum Onkologii w Szczecinie
- BioVirtus Centrum Medyczne
- Summit Clinical Research s.r.o.
- Northern Centre for Cancer Care
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
no name
Arm Description
Group 1: patients with normal hepatic function Group 2: patients who have moderate hepatic impairment
Outcomes
Primary Outcome Measures
Maximum plasma rucaparib concentration (Cmax)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
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
Secondary Outcome Measures
Area under the plasma rucaparib concentration-time curve from time zero up to time infinity (AUC0-inf)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Terminal half-life (t1/2) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time to attain maximum plasma rucaparib concentration (Tmax)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Apparent clearance (CL/F) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Apparent volume of distribution during terminal phase (Vz/F) of rucaparib
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Trough plasma concentration of rucaparib at steady state (Cmin,ss)
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Renal clearance (CLR) of rucaparib
PK parameter of rucaparib to be calculated from the plasma and urine concentration-time data
Cumulative amount of rucaparib excreted in urine during urine collection period post rucaparib dose
PK parameter of rucaparib to be calculated based on urine concentration-time data
Fraction of administered rucaparib excreted into urine (Fe/F) during urine collection period post rucaparib dose
PK parameter of rucaparib to be calculated based on the amount of rucaparib recovered in urine
Incidence of Adverse Events [Safety and Tolerability]
Incidence of clinical laboratory abnormalities [Safety and Tolerability]
Incidence of dose modifications [Safety and Tolerability]
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03521037
Brief Title
Rucaparib Hepatic Impairment Study in Patients With a Solid Tumor
Official Title
A Phase 1, Open-Label, Parallel Group Study to Determine the Pharmacokinetics, Safety and Tolerability of Rucaparib in Patients With an Advanced Solid Tumor and Either Moderate Hepatic Impairment or Normal Hepatic Function
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
February 27, 2018 (Actual)
Primary Completion Date
September 27, 2019 (Actual)
Study Completion Date
February 24, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
pharmaand GmbH
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
Detailed Description
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. The starting dose for all Group 1 patients will be 600 mg BID. The first 2 patients with moderate hepatic impairment (Group 2) that enter Part II will receive a starting dose of 400 mg BID rucaparib; a lower dose of rucaparib may also be set based on PK results observed in Part I. If this initial starting dose is determined to be safe and tolerable as determined by real-time PK data and dose limiting toxicities (DLT) observed during the first 28 days of rucaparib, the starting dose of rucaparib may be increased in subsequent Group 2 patients. The starting dose for Group 2 patients may also be lowered, based on the patients' real time PK and emerging safety data. The Sponsor and key clinical research organization (CRO) staff will review available adverse event, laboratory, and PK data to determine the starting dose for subsequent Group 2 patients, as well as allowing intra-patient dose escalation of rucaparib after Cycle 1.Treatment with rucaparib will continue until progression of disease, unacceptable toxicity, death, loss to follow-up, withdrawal of consent, or other appropriate clinical reason for discontinuation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms
Keywords
rucaparib, CO-338, Clovis, Clovis Oncology, PARP inhibitor, hepatic impairment
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
no name
Arm Type
Experimental
Arm Description
Group 1: patients with normal hepatic function Group 2: patients who have moderate hepatic impairment
Intervention Type
Drug
Intervention Name(s)
Rucaparib camsylate
Other Intervention Name(s)
rubraca
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum plasma rucaparib concentration (Cmax)
Description
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time Frame
day 1 to day 7
Title
Area under the plasma rucaparib concentration-time curve from time zero up to the last time point with quantifiable concentration (AUC0-last)
Description
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time Frame
day 1 to day 7
Secondary Outcome Measure Information:
Title
Area under the plasma rucaparib concentration-time curve from time zero up to time infinity (AUC0-inf)
Description
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time Frame
day 1 to day 7
Title
Terminal half-life (t1/2) of rucaparib
Description
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time Frame
day 1 to day 7
Title
Time to attain maximum plasma rucaparib concentration (Tmax)
Description
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time Frame
day 1 to day 7
Title
Apparent clearance (CL/F) of rucaparib
Description
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time Frame
day 1 to day 7
Title
Apparent volume of distribution during terminal phase (Vz/F) of rucaparib
Description
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time Frame
day 1 to day 7
Title
Trough plasma concentration of rucaparib at steady state (Cmin,ss)
Description
PK parameter of rucaparib to be calculated from the plasma concentration-time data
Time Frame
approximately 4 months
Title
Renal clearance (CLR) of rucaparib
Description
PK parameter of rucaparib to be calculated from the plasma and urine concentration-time data
Time Frame
day 1 to day 2
Title
Cumulative amount of rucaparib excreted in urine during urine collection period post rucaparib dose
Description
PK parameter of rucaparib to be calculated based on urine concentration-time data
Time Frame
day 1 to day 2
Title
Fraction of administered rucaparib excreted into urine (Fe/F) during urine collection period post rucaparib dose
Description
PK parameter of rucaparib to be calculated based on the amount of rucaparib recovered in urine
Time Frame
day 1 to day 2
Title
Incidence of Adverse Events [Safety and Tolerability]
Time Frame
From Day 1 to last patient visit in Part II (approximately 2 years)
Title
Incidence of clinical laboratory abnormalities [Safety and Tolerability]
Time Frame
From Day 1 to last patient visit in Part II (approximately 2 years)
Title
Incidence of dose modifications [Safety and Tolerability]
Time Frame
From Day 1 to last patient visit in Part II (approximately 2 years)
Other Pre-specified Outcome Measures:
Title
Maximum plasma metabolite concentration (Cmax)
Description
PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data
Time Frame
day 1 to day 7
Title
Area under the plasma metabolite concentration-time curve from time zero up to the last time point with quantifiable concentrations (AUC0-last)
Description
PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data
Time Frame
day 1 to day 7
Title
Area under the plasma metabolite concentration-time curve from time zero up to time infinity (AUC0-inf)
Description
PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data
Time Frame
day 1 to day 7
Title
Terminal half-life (t1/2) of metabolite
Description
PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data
Time Frame
day 1 to day 7
Title
Time to attain maximum plasma metabolite concentration (Tmax)
Description
PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data
Time Frame
day 1 to day 7
Title
Plasma trough concentration of metabolite(s) at steady state (Cmin,ss)
Description
PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data
Time Frame
day 1 to day 7
Title
Renal clearance (CLR) of metabolite(s)
Description
PK parameters for rucaparib metabolite(s) to be calculated from plasma and urine concentration-time data
Time Frame
day 1 to day 2
Title
Cumulative amount of rucaparib metabolite(s) excreted in urine during urine collection period post rucaparib dose
Description
PK parameter for rucaparib metabolite(s) to be calculated from urine concentration-time data
Time Frame
day 1 to day 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
Exclusion Criteria:
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;
Acute damage of the liver with Grade 4 AST/ALT values
Facility Information:
Facility Name
Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej
City
Biała Podlaska
ZIP/Postal Code
21-500
Country
Poland
Facility Name
Med Polonia Sp. z o.o.
City
Poznań
ZIP/Postal Code
60-693
Country
Poland
Facility Name
Zachodniopomorskie Centrum Onkologii w Szczecinie
City
Szczecin
ZIP/Postal Code
71-730
Country
Poland
Facility Name
BioVirtus Centrum Medyczne
City
Warszawa
ZIP/Postal Code
02-681
Country
Poland
Facility Name
Summit Clinical Research s.r.o.
City
Bratislava
ZIP/Postal Code
831 01
Country
Slovakia
Facility Name
Northern Centre for Cancer Care
City
Newcastle Upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Rucaparib Hepatic Impairment Study in Patients With a Solid Tumor
We'll reach out to this number within 24 hrs