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

Hepatic Insufficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01273493
• Other study ID #: CR017542
• Secondary ID: ET7430OVC1004
• Status: Completed
• Phase: Phase 1
• First received: December 23, 2010
• Last updated: February 12, 2016
• Start date: December 2010
• Est. completion date: April 2014

Study information

• Verified date: February 2016
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatic Insufficiency
• Liver Diseases
• Neoplasm Metastases
• Neoplasm Metastasis

Intervention

Drug:
• Trabectedin
Trabectedin 0.58 or 1.3 mg/m^2 (or adjusted dose) i.v. will be administered on Day 1.
• Dexamethasone
Dexamethasone will be administered as 20 mg/m^2, 30 minutes prior to trabectedin.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC	PharmaMar

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of trabectedin		At protocol-specified time points for up to 8 days	No
Secondary	Number of patients with adverse events		Up to 30 days after the administration of trabectedin	No
Secondary	Findings from clinical laboratory evaluations		Up to 30 days after the administration of trabectedin	No
Secondary	Findings from vital signs measurements		Up to 30 days after the administration of trabectedin	No
Secondary	Findings from physical examinations		Up to 30 days after the administration of trabectedin	No
Secondary	Evaluate survival data		at a time point to be determined by the sponsor at a later date.	No

External Links

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