Clinical trial NCT01273493: A Pharmacokinetic Study of Trabectedin in Patients With Advanced Malignancies and Hepatic Dysfunction
Official title: An Open-Label, Multicenter, Pharmacokinetic Study of Trabectedin in Subjects With Advanced Malignancies and Hepatic Dysfunction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasm Metastases
Hepatic Insufficiency
Keywords: Trabectedin, YONDELIS
Antineoplastic Agents
Solid tumors
Locally advanced or metastatic disease
Chemotherapy
Pharmacokinetics
Hepatic Dysfunction
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: PharmaMar
First posted: 2011-01-10
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Pharmacokinetics of trabectedin
timeFrame: At protocol-specified time points for up to 8 days
Secondary outcomes:
measure: Number of patients with adverse events
timeFrame: Up to 30 days after the administration of trabectedin
measure: Findings from clinical laboratory evaluations
timeFrame: Up to 30 days after the administration of trabectedin
measure: Findings from vital signs measurements
timeFrame: Up to 30 days after the administration of trabectedin
measure: Findings from physical examinations
timeFrame: Up to 30 days after the administration of trabectedin
measure: Evaluate survival data
timeFrame: at a time point to be determined by the sponsor at a later date.
Other outcomes:
Locations:
city: Scottsdale
country: United States
state: Arizona
city: Detroit
country: United States
state: Michigan
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Salt Lake City
country: United States
state: Utah
city: Tacoma
country: United States
state: Washington
city: Edegem
country: Belgium
city: Wilrijk
country: Belgium
city: Edmonton
country: Canada
state: Alberta
city: Barcelona
country: Spain
city: Madrid
country: Spain
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.