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

Purpose

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.

Condition	Intervention	Phase
Neoplasm Metastases	Drug: Sequence 1 Drug: Sequence 2	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label, Multicenter Study to Assess the Potential Effects of Rifampin on the Pharmacokinetics of Trabectedin in Subjects With Advanced Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone sodium phosphate Rifampin

U.S. FDA Resources

Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	8
Study Start Date:	December 2010
Estimated Study Completion Date:	February 2013
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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: 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.	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. 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.

Arms

Assigned Interventions

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.

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: 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.

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.

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.

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01273480

Contacts

Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions:

JNJ.CT@sylogent.com

Locations

United States, Pennsylvania
	Recruiting
Philadelphia, Pennsylvania, United States
United States, Utah
	Active, not recruiting
Salt Lake City, Utah, United States

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

Study Director:

Janssen Research & Development, LLC C. Clinical Trial

Janssen Research & Development, LLC

More Information

Additional Information:

To learn how to participate in this trial please click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:	NCT01273480 History of Changes
Other Study ID Numbers:	CR017536, ET743OVC1002
Study First Received:	December 23, 2010
Last Updated:	January 15, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:

Trabectedin, YONDELIS
Rifampin (RIFADIN)
Antineoplastic Agents
Solid tumors

Locally advanced or metastatic disease
Chemotherapy
Pharmacokinetics

Additional relevant MeSH terms:

Neoplasms
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Trabectedin
Antineoplastic Agents
Dexamethasone
Rifampin
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on May 19, 2013