A Study to Assess the Potential Effects of Rifampin on the Pharmacokinetics of Trabectedin in Patients With Advanced Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01273480
First received: December 23, 2010
Last updated: June 3, 2013
Last verified: June 2013

December 23, 2010
June 3, 2013
December 2010
October 2012   (final data collection date for primary outcome measure)
  • Pharmacokinetics of trabectedin [ Time Frame: At protocol-specified time points up to 8 days during each 28-day cycle in Sequence 1 and up to 6 days during each 28-day cycle in Sequence 2 ] [ Designated as safety issue: No ]
  • Pharmacokinetics of rifampin [ Time Frame: 1 day during Sequence 1 and Sequence 2 after rifampin is coadministered with trabectedin ] [ Designated as safety issue: No ]
  • Pharmacokinetics of trabectedin [ Time Frame: At protocol-specified time points up to 8 days during each 28-day cycle in Sequence 1 and up to 6 days during each 28 day cycle in Sequence 2 ] [ Designated as safety issue: No ]
  • Pharmacokinetics of rifampin [ Time Frame: 1 day during Sequence 1 and Sequence 2 after rifampin is coadministered with trabectedin ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01273480 on ClinicalTrials.gov Archive Site
  • Number of patients with adverse events [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: Yes ]
  • Findings from clinical laboratory evaluations [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Findings from vital signs measurements [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Findings from physical examinations [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Number of patients with adverse events [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: Yes ]
  • Findings from clinical laboratory evaluations [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Findings from vital signs measurements [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Findings from physical examinations [ Time Frame: Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin ] [ Designated as safety issue: No ]
  • Evaluation of survival data [ Time Frame: At a time point to be determined by the sponsor at a later date ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study to Assess the Potential Effects of Rifampin on the Pharmacokinetics of Trabectedin in Patients With Advanced Malignancies
An Open-Label, Multicenter Study to Assess the Potential Effects of Rifampin on the Pharmacokinetics of Trabectedin in Subjects With Advanced Malignancies

The purpose of this study is to evaluate the potential effects of rifampin on blood levels of trabectedin after administration to patients with advanced malignancies.

This is an open-label study (patients will know the names of the study drugs they receive), randomized (patients will be assigned 1 of 2 treatment sequences by chance) that is designed to examine the pharmacokinetics (blood levels) and to assess survival and safety of trabectedin when coadministered with rifampin in patients with advanced malignancies. Study drugs include trabectedin and rifampin. Trabectedin is a drug being developed to treat patients with cancer that will be administered intravenously (i.v.) through a catheter (tube) into a central vein over a period of 3 hours once every 28 days with and without rifampin. Rifampin is an antibiotic that may interfere with the action of trabectedin that will be taken orally (by mouth) as capsules. In addition, dexamethasone, a drug used to prevent nausea and vomiting in chemotherapy patients that may have protective effects on the liver, will be administered to patients before the administration of trabectedin. In the study, 3 patients will initially be randomized sequentially to Treatment Sequence 1 or Treatment Sequence 2 to evaluate safety. If the safety and pharmacokinetic data collected from these 3 patients is deemed acceptable, additional patients will be randomized to 1 of 2 treatment sequences. Patients who complete the treatment phase of the study or who are discontinued due to rifampin toxicity, and who in the opinion of the investigator would derive an overall clinical benefit from further treatment with trabectedin, will have the opportunity to continue treatment with trabectedin in the optional extension phase. The dose and schedule of trabectedin may be modified by the treating physician in the optional extension phase to be more appropriate for the type of malignancy being treated. Patients will receive 20 mg of i.v. dexamethasone (or its equivalent) prior to trabectedin administration in all cycles. Patients randomized to Sequence 1 will receive rifampin 600mg 1X daily(6 doses)+trabectedin 1.3 mg/m2 i.v. followed 28 days later by trabectedin 1.3 mg/m2 i.v. Patients randomized to Sequence 2 will receive trabectedin 1.3 mg/m2 i.v. followed 28 days later by rifampin 600mg 1X daily(6 doses)+trabectedin 1.3mg/m2 i.v. Dexamethasone 20 mg i.v., or equivalent will be administered 30 minutes prior to trabectedin administration.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Neoplasm Metastases
  • Drug: Sequence 1
    Cycle 1: 2 rifampin 300 mg capsules 1x daily for 5 days followed by 2 rifampin capsules prior to trabectedin 1.3 mg/m2 i.v. on Day 1 followed 28 days later by cycle 2 trabectedin 1.3 mg/m2 i.v. on Day 1. Dexamethasone 20 mg i.v. administered prior to trabectedin in each cycle.
  • Drug: Sequence 2
    Cycle 1: Trabectedin 1.3 mg/m2 i.v. on Day 1 followed by 2 rifampin 300 mg capsules once daily on Days 24-28 followed by Cycle 2, 2 rifampin capsules prior to trabectedin 1.3 mg/m2 i.v. on Day 1 of Cycle 2. Dexamethasone 20 mg i.v. administered prior to trabectedin in each cycle.
  • Experimental: 002
    Sequence 2 Cycle 1: Trabectedin 1.3 mg/m2 i.v. on Day 1 followed by 2 rifampin 300 mg capsules once daily on Days 24-28 followed by Cycle 2 2 rifampin capsules prior to trabectedin 1.3 mg/m2 i.v. on Day 1 of Cycle 2. Dexamethasone 20 mg i.v. administered prior to trabectedin in each cycle.
    Interventions:
    • Drug: Sequence 1
    • Drug: Sequence 2
  • Experimental: 001
    Sequence 1 Cycle 1: 2 rifampin 300 mg capsules 1x daily for 5 days followed by 2 rifampin capsules prior to trabectedin 1.3 mg/m2 i.v. on Day 1 followed 28 days later by cycle 2 trabectedin 1.3 mg/m2 i.v. on Day 1. Dexamethasone 20 mg i.v. administered prior to trabectedin in each cycle.
    Interventions:
    • Drug: Sequence 2
    • Drug: Sequence 1
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
October 2012
October 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with locally advanced or metastatic disease, any solid tumor except hepatocellular carcinoma, who have relapsed or had progressive disease following standard of care treatment with chemotherapy prior to enrollment, or intolerant to prior standard of care treatment with chemotherapy
  • Patients with Eastern Cooperative Oncology Group (ECOG) score of <=2
  • Patients able to receive dexamethasone
  • Patients with hepatic function variables: total bilirubin <=upper limit of normal (ULN), alkaline phosphatase (ALP) <=1.5 ULN and liver function test results (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) of <=2.5x ULN

Exclusion Criteria:

  • Patients with previous exposure to trabectedin
  • Patients with cancer that has metastasized (spread) to the central nervous system
  • Patients with known liver disease
  • Patients who had a myocardial infarct (heart attack) within 6 months before enrollment or who have any other clinically significant or unstable medical condition as assessed by the Investigator
  • Patients unable to have a central catheter
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01273480
CR017536, ET743OVC1002
Yes
Janssen Research & Development, LLC
Janssen Research & Development, LLC
Not Provided
Study Director: Janssen Research & Development, LLC C. Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP