Trial Information

An Open-Label, Multicenter Study to Assess the Potential Effects of Rifampin 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 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.