A Pharmacokinetic Study of Trabectedin in Patients With Advanced Malignancies and Hepatic Dysfunction

NCT ID: NCT01273493

Last Updated: 2016-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2014-04-30

Brief Summary

The purpose of this study is to characterize the pharmacokinetics (blood levels) of trabectedin after administration to patients with advanced malignancies and hepatic (liver) dysfunction.

Detailed Description

This is an open-label (patients will know the names of study drugs they receive), single-dose, study that will examine the pharmacokinetics (blood levels) and assess survival and safety of trabectedin in patients with advanced malignancies who either have hepatic (liver) dysfunction or do not have hepatic dysfunction (patients enrolled without hepatic dysfunction will be referred to as the control group). 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. 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. Patients who complete the treatment phase of the study 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. A single dose of trabectedin (1.3 mg/m2 in patients in the control group and 0.58 mg/m2 in patients with hepatic dysfunction) will be administered by i.v.infusion over a 3-hour period. The dose of trabectedin may be adjusted if necessary for patients with hepatic dysfunction subsequently enrolled in the study. All patients will be administered dexamethasone 20 mg i.v. (or equivalent) approximately 30 minutes before the administration of trabectedin.

Conditions

Neoplasm Metastases; Hepatic Insufficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trabectedin 1.3 mg/m^2 plus Dexamethasone

Control group Trabectedin 1.3 mg/m\^2 i.v.will be administered on Day 1. Dexamethasone will be administered 30 minutes prior to trabectedin.

Group Type: EXPERIMENTAL

Trabectedin

Intervention Type: DRUG

Trabectedin 0.58 or 1.3 mg/m\^2 (or adjusted dose) i.v. will be administered on Day 1.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered as 20 mg/m\^2, 30 minutes prior to trabectedin.

Trabectedin 0.58 mg/m^2 plus Dexamethasone

Hepatic dysfunction group Trabectedin 0.58 mg/m\^2 (or adjusted dose) i.v. will be administered on Day 1. Dexamethasone will be administered 30 minutes prior to trabectedin.

Group Type: EXPERIMENTAL

Trabectedin

Intervention Type: DRUG

Trabectedin 0.58 or 1.3 mg/m\^2 (or adjusted dose) i.v. will be administered on Day 1.

Dexamethasone

Intervention Type: DRUG

Dexamethasone will be administered as 20 mg/m\^2, 30 minutes prior to trabectedin.

Interventions

Trabectedin

Trabectedin 0.58 or 1.3 mg/m\^2 (or adjusted dose) i.v. will be administered on Day 1.

Intervention Type: DRUG

Dexamethasone

Dexamethasone will be administered as 20 mg/m\^2, 30 minutes prior to trabectedin.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with locally advanced or metastatic disease, any solid tumor except hepatocellular carcinoma, who have been previously treated with systemic chemotherapy (chemotherapy administered through the blood) and who have had 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 at the time of screening
• Patients enrolled with hepatic dysfunction must have laboratory test results for total bilirubin of >1.5x to <=3x the upper limit of normal (ULN) and liver function tests (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) of <8x the ULN
• Patients enrolled without hepatic dysfunction must have laboratory test results for total bilirubin of less than the ULN, alkaline phosphatase (ALP) <=1.5x the ULN, and AST and ALT of <=the ULN.

Exclusion Criteria

• Patients with previous exposure to trabectedin
• Patients with known liver disease
• Patients diagnosed with hepatocellular carcinoma, or who have a history of biliary sepsis within the past 2 years
• Patients unwilling to have a central catheter
• In hepatic dysfunction group, patients with hepatic dysfunction who have Gilbert's syndrome. Patients signs of encephalopathy (altered brain function).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC C. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Scottsdale, Arizona, United States

Detroit, Michigan, United States

New York, New York, United States

Philadelphia, Pennsylvania, United States

Salt Lake City, Utah, United States

Tacoma, Washington, United States

Edegem, , Belgium

Wilrijk, , Belgium

Edmonton, Alberta, Canada

Barcelona, , Spain

Madrid, , Spain

Countries

United States; Belgium; Canada; Spain

References

Calvo E, Azaro A, Rodon J, Dirix L, Huizing M, Senecal FM, LoRusso P, Yee L, Poggesi I, de Jong J, Triantos S, Park YC, Knoblauch RE, Parekh TV, Demetri GD, von Mehren M. Hepatic safety analysis of trabectedin: results of a pharmacokinetic study with trabectedin in patients with hepatic impairment and experience from a phase 3 clinical trial. Invest New Drugs. 2018 Jun;36(3):476-486. doi: 10.1007/s10637-017-0546-9. Epub 2017 Nov 27.

Reference Type: DERIVED

PMID: 29177975 (View on PubMed)

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=872&filename=CR017542_CSR.pdf

An Open-Label, Multicenter, Pharmacokinetic Study of Trabectedin in Subjects with Advanced Malignancies and Hepatic Dysfunction

Other Identifiers

ET7430OVC1004

Identifier Type: OTHER

Identifier Source: secondary_id

CR017542

Identifier Type: -

Identifier Source: org_study_id