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Rucaparib Hepatic Impairment Study in Patients With a Solid Tumor

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ClinicalTrials.gov Identifier: NCT03521037
Recruitment Status : Recruiting
First Posted : May 10, 2018
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.

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).

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Rucaparib camsylate Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : March 31, 2018
Estimated Primary Completion Date : August 31, 2019
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Rucaparib

Arm Intervention/treatment
Experimental: no name
Group 1: patients with normal hepatic function Group 2: patients who have moderate hepatic impairment
Drug: Rucaparib camsylate
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.
Other Name: rubraca




Primary Outcome Measures :
  1. Maximum plasma rucaparib concentration (Cmax) [ Time Frame: day 1 to day 7 ]
    PK parameter of rucaparib to be calculated from the plasma concentration-time data

  2. Area under the plasma rucaparib concentration-time curve from time zero up to the last time point with quantifiable concentration (AUC0-last) [ Time Frame: day 1 to day 7 ]
    PK parameter of rucaparib to be calculated from the plasma concentration-time data


Secondary Outcome Measures :
  1. Area under the plasma rucaparib concentration-time curve from time zero up to time infinity (AUC0-inf) [ Time Frame: day 1 to day 7 ]
    PK parameter of rucaparib to be calculated from the plasma concentration-time data

  2. Terminal half-life (t1/2) of rucaparib [ Time Frame: day 1 to day 7 ]
    PK parameter of rucaparib to be calculated from the plasma concentration-time data

  3. Time to attain maximum plasma rucaparib concentration (Tmax) [ Time Frame: day 1 to day 7 ]
    PK parameter of rucaparib to be calculated from the plasma concentration-time data

  4. Apparent clearance (CL/F) of rucaparib [ Time Frame: day 1 to day 7 ]
    PK parameter of rucaparib to be calculated from the plasma concentration-time data

  5. Apparent volume of distribution during terminal phase (Vz/F) of rucaparib [ Time Frame: day 1 to day 7 ]
    PK parameter of rucaparib to be calculated from the plasma concentration-time data

  6. Trough plasma concentration of rucaparib at steady state (Cmin,ss) [ Time Frame: approximately 4 months ]
    PK parameter of rucaparib to be calculated from the plasma concentration-time data

  7. Renal clearance (CLR) of rucaparib [ Time Frame: day 1 to day 2 ]
    PK parameter of rucaparib to be calculated from the plasma and urine concentration-time data

  8. Cumulative amount of rucaparib excreted in urine during urine collection period post rucaparib dose [ Time Frame: day 1 to day 2 ]
    PK parameter of rucaparib to be calculated based on urine concentration-time data

  9. Fraction of administered rucaparib excreted into urine (Fe/F) during urine collection period post rucaparib dose [ Time Frame: day 1 to day 2 ]
    PK parameter of rucaparib to be calculated based on the amount of rucaparib recovered in urine

  10. Incidence of Adverse Events [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]
  11. Incidence of clinical laboratory abnormalities [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]
  12. Incidence of dose modifications [Safety and Tolerability] [ Time Frame: From Day 1 to last patient visit in Part II (approximately 2 years) ]

Other Outcome Measures:
  1. Maximum plasma metabolite concentration (Cmax) [ Time Frame: day 1 to day 7 ]
    PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data

  2. Area under the plasma metabolite concentration-time curve from time zero up to the last time point with quantifiable concentrations (AUC0-last) [ Time Frame: day 1 to day 7 ]
    PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data

  3. Area under the plasma metabolite concentration-time curve from time zero up to time infinity (AUC0-inf) [ Time Frame: day 1 to day 7 ]
    PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data

  4. Terminal half-life (t1/2) of metabolite [ Time Frame: day 1 to day 7 ]
    PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data

  5. Time to attain maximum plasma metabolite concentration (Tmax) [ Time Frame: day 1 to day 7 ]
    PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data

  6. Plasma trough concentration of metabolite(s) at steady state (Cmin,ss) [ Time Frame: day 1 to day 7 ]
    PK parameter for rucaparib metabolite(s) to be calculated from plasma concentration-time data

  7. Renal clearance (CLR) of metabolite(s) [ Time Frame: day 1 to day 2 ]
    PK parameters for rucaparib metabolite(s) to be calculated from plasma and urine concentration-time data

  8. Cumulative amount of rucaparib metabolite(s) excreted in urine during urine collection period post rucaparib dose [ Time Frame: day 1 to day 2 ]
    PK parameter for rucaparib metabolite(s) to be calculated from urine concentration-time data



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03521037


Contacts
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Contact: Alex McNees +1 415-409-5440 amcnees@clovisoncology.com

Locations
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Poland
Wojewódzki Szpital Specjalistyczny w Białej Podlaskiej Recruiting
Biała Podlaska, Poland, 21-500
Contact: Piotr Centkowski         
Med Polonia Sp. z o.o. Recruiting
Poznań, Poland, 60-693
Contact: Rodryg Ramlau         
Zachodniopomorskie Centrum Onkologii w Szczecinie Recruiting
Szczecin, Poland, 71-730
Contact: Dorota Nowak         
BioVirtus Centrum Medyczne Recruiting
Warszawa, Poland, 02-681
Contact: Monika Tomaszewska-Kiecana, MD    48 22 545.84.64      
Slovakia
Summit Clinical Research s.r.o. Recruiting
Bratislava, Slovakia, 831 01
Contact: Miriam Drahokoupilova         
United Kingdom
Northern Centre for Cancer Care Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Contact: Yvette Drew         
Sponsors and Collaborators
Clovis Oncology, Inc.

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Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT03521037     History of Changes
Other Study ID Numbers: CO-338-078
First Posted: May 10, 2018    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Clovis Oncology, Inc.:
rucaparib
CO-338
Clovis
Clovis Oncology
PARP inhibitor
hepatic impairment

Additional relevant MeSH terms:
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Liver Diseases
Digestive System Diseases
Rucaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents