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Trial record 2 of 14 for:    rucaparib

Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib (AME)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Clovis Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02986100
First received: November 14, 2016
Last updated: December 5, 2016
Last verified: November 2016
  Purpose
The purpose of this study is to characterize the mass balance, absorption, metabolism, and elimination pathways of orally administered [14C] rucaparib followed by cycle by cycle treatment with rucaparib continuing until disease progression or other reason for discontinuation

Condition Intervention Phase
Solid Tumor
Drug: C-14 labeled Rucaparib
Drug: Rucaparib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: An Open-Label, Non-Randomized, Phase I Study to Assess the Absorption, Metabolism, and Excretion Following a Single Oral Dose of [14C]-Rucaparib in Patients With Advanced Solid Tumors

Further study details as provided by Clovis Oncology, Inc.:

Primary Outcome Measures:
  • Pharmacokinetics of 14C-labeled rucaparib (radioactivity in whole blood and plasma): tmax [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Time to peak concentration (tmax)

  • Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): Cmax [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    peak (maximum) concentration (Cmax)

  • Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): t1/2 [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Elimination half-life (t1/2)

  • Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): AUC [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Area under curve (AUC)

  • Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): CL/F [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Oral clearance (CL/F)

  • Pharmacokinetics of 14C-labeled rucaparib(Radioactivity in whole blood and plasma): V/F [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Apparent volume of distribution (V/F)

  • Excretion rate of 14C-labeled rucaparib(radioactivity in feces) [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Percent of dose excreted in feces

  • Excretion rate of 14C-labeled rucaparib(radioactivity in urine) [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Percent of dose excreted in urine

  • Pharmacokinetics of rucaparib (in urine): CLR [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Renal clearance (CLR)

  • Excretion rate of 14C-labeled rucaparib(radioactivity in vomit, if applicable) [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    Percent of dose in vomit, if applicable

  • Metabolite identification of rucaparib in plasma, urine and feces [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
  • Cumulative whole blood:plasma ratio calculated for Cmax [ Time Frame: Days 1-13 ] [ Designated as safety issue: No ]
    peak concentration (Cmax)

  • Cumulative whole blood:plasma ratio calculated for AUC0-tlast [ Time Frame: Day 1-13 ] [ Designated as safety issue: No ]
    AUC from time zero to the last time point with concentration above the lower limit of quantitation (AUC0-last)

  • Cumulative whole blood:plasma ratio calculated for AUCinf [ Time Frame: Day 1-13 ] [ Designated as safety issue: No ]
    AUC from time zero to infinity (AUCinf)


Secondary Outcome Measures:
  • Tolerability and safety of rucaparib assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications [ Time Frame: From cycle 1 Day 1 until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks ] [ Designated as safety issue: Yes ]
    Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications


Other Outcome Measures:
  • To evaluate the antitumor activity of rucaparib in BRCA mutated solid tumors based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Cycle 1 Day 1 until progression of disease, unacceptable toxicity, or discontinuation for other reasons ] [ Designated as safety issue: No ]
    Response will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and tumor markers per applicable criteria for a given tumor type


Estimated Enrollment: 6
Study Start Date: November 2016
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: C-14 labeled rucaparib

Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met.

After completion of Part I, patients with a deleterious BRCA mutation will have the option to participate in Part II by receiving 600 mg BID rucaparib tablets orally in 28 day cycles until disease progression, unacceptable toxicity, death, or discontinuation for other reasons

Drug: C-14 labeled Rucaparib
Each dosage unit consists of a hard gelatin capsule filled with cold rucaparib camsylate and [14C]-rucaparib camsylate salt. Each capsule contains approximately 150 mg rucaparib (free base weight) and approximately 35 µCi of [14C]-rucaparib. Each patient will ingest four capsules in the fasted state for a total dose of 600 mg rucaparib (free base weight) with approximately 140 µCi of [14C]-rucaparib
Drug: Rucaparib
200 & 300 mg tablet
Other Name: CO-338

Detailed Description:

This is a Phase 1, open-label, non-randomized, mass balance study in patients with histologically or cytologically confirmed advanced solid tumors. Approximately 6 patients will be enrolled. The study will consist of 2 parts: a mass balance part (Part I) and a rucaparib treatment part (Part II).

Each patient will receive a single oral dose of 600 mg [14C] rucaparib (approximately 140 µCi) in the fasted state. Patients will be confined at the study site for the collection of blood samples and excreta for a maximum of 13 days, from Day -1. The patient can be discharged sooner than Day 13, if the discharge criteria are met. If the cumulative recovery of radioactivity exceeds 90% of the administered dose or if radioactivity in urine and feces is < 1% of the administered dose over a 24 hour period on two consecutive days, as determined by quick counts.

In Part II, the treatment with rucaparib in 28-day cycles will continue until progression of disease, unacceptable toxicity, or other reason for discontinuation.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed advanced solid tumor
  • Part II only: Have a known deleterious BRCA1/2 mutation (germline or somatic) as determined by a local or central laboratory
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate bone marrow, renal, and liver function

Exclusion Criteria:

  • Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, or angiogenesis inhibitors within 14 days prior to Day 1
  • Participation in a trial involving administration of [14C]-labeled compound(s) within the last 6 months prior to Day 1
  • Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months prior to Screening
  • Pre-existing duodenal stent, recent or existing bowel obstruction, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib
  • Untreated or symptomatic central nervous system (CNS) metastases
  • Evidence or history of bleeding disorder
  • Participation in another investigational drug trial within 14 days prior to Day 1 (or 5 times the half-life of the drug, whichever is longer) or exposure to more than three new investigational agents within 12 months prior to Day 1
  • Acute illness (eg, nausea, vomiting, fever, diarrhea) within 14 days prior to Day 1, unless mild in severity and approved by the Investigator and Sponsor's/designated medical representative
  • Active second malignancy
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02986100

Contacts
Contact: Clovis Oncology Clinical Trial Information 1-855-262-3040 (USA) clovistrials@emergingmed.com
Contact: Clovis Oncology Clinical Trial Information +1 303-625-5160 (Ex-US) clovistrials@emergingmed.com

Locations
Hungary
PRA Magyarország Kft. Recruiting
Budapest, Rottenbiller utca 13, Hungary, 1077
Contact: Zsuzsanna Pápai, MD    +36 30 828 1059    zspapai@gmail.com   
Sponsors and Collaborators
Clovis Oncology, Inc.
  More Information

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02986100     History of Changes
Other Study ID Numbers: CO-338-045  2015-004394-32 
Study First Received: November 14, 2016
Last Updated: December 5, 2016
Health Authority: European Union: European Medicines Agency
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Clovis Oncology, Inc.:
rucaparib
CO-338
Clovis
Clovis Oncology
PARP inhibitor
Absorption
Metabolism
Excretion

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

ClinicalTrials.gov processed this record on December 08, 2016