Trial Information

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

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 ketoconazole in patients with advanced malignancies.
Study drugs include trabectedin and ketoconazole. Trabectdin 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 21 days with and without
Ketoconazole. Ketoconazole is an antifungal agent that may interfere with the action of
trabectedin when taken orally (by mouth) as tablets. In addition, dexamethosone, 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 each
treatment cycle. This study will consist of 2 parts, Part A and B. In Part A, trabectedin
will be administered with ketoconazole to 3 patients to evaluate safety. If the safety and
PK data collected in Part A is deemed acceptable, enrollment in Part B of the study will
begin and patients will receive 1 of 2 treatment sequences of trabectedin and ketoconazole.
Patients in Part A and Part B who complete the treatment phase of the study or who are
discontinued due to ketoconazole 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. Part A consists of ketoconazole 200mg 2x daily+trabectedin
0.2mg/m2 i.v. followed 21 days later by trabectedin 1.3mg/m2 i.v. Part B consists of
Sequence 1 (ketoconazole 200mg 2x daily+trabectedin 0.2mg/m2 i.v.followed 21 days later by
trabectedin 1.3mg/m2 i.v.) and Sequence 2 (trabectedin 1.3mg/m2 i.v followed 21 days later
by ketoconazole 200mg 2x daily+trabectedin 0.2mg/m2 i.v). Dexamethasone 20mg i.v. or
equivalent, will be given 30 minutes before trabectedin in each cycle.