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

NCT01273480 | Completed Phase 1 DMC

• 2 other identifiers: CR017536ET743OVC1002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Neoplasm Metastases

Keywords

Trabectedin, YONDELIS; Rifampin (RIFADIN); Antineoplastic Agents; Solid tumors; Locally advanced or metastatic disease; Chemotherapy; Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics of trabectedin

  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

• Pharmacokinetics of rifampin

  1 day during Sequence 1 and Sequence 2 after rifampin is coadministered with trabectedin

Secondary Outcomes (4)

• Number of patients with adverse events

  Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin

• Findings from clinical laboratory evaluations

  Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin

• Findings from vital signs measurements

  Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin

• Findings from physical examinations

  Time from 1st dose of trabectedin up to 30 days after the last dose of trabectedin

Study Arms (2)

002

EXPERIMENTAL

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.

Drug: Sequence 1; Drug: Sequence 2

001

EXPERIMENTAL

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; Drug: Sequence 1

Interventions

Sequence 1 DRUG

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.

002

Sequence 2 DRUG

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.

001

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (2)

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Related Publications (1)

• Machiels JP, Staddon A, Herremans C, Keung C, Bernard A, Phelps C, Khokhar NZ, Knoblauch R, Parekh TV, Dirix L, Sharma S. Impact of cytochrome P450 3A4 inducer and inhibitor on the pharmacokinetics of trabectedin in patients with advanced malignancies: open-label, multicenter studies. Cancer Chemother Pharmacol. 2014 Oct;74(4):729-37. doi: 10.1007/s00280-014-2554-1. Epub 2014 Aug 7.

  PMID: 25100135 DERIVED

Related Links

• An Open-Label, Multicenter Study to Assess the Potential Effects of Rifampin on the Pharmacokinetics of Trabectedin in Subjects With Advanced Malignancies

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Janssen Research & Development, LLC C. Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: January 10, 2011
• Study Start: December 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: November 25, 2014

Record last verified: 2014-11

Locations

US (2)