A Placebo-Controlled Study Evaluating the Potential Effects of Trabectedin on the Heart in Patients With Advanced Cancer

The purpose of the study is to determine the effects of trabectedin on the heart's electrical cycle as measured by an electrocardiogram in patients with advanced cancer. The study will also assess the safety of trabectedin and the way trabectedin is used by the body in patients with advanced cancer.

This is a single-blind, placebo-controlled study to evaluate the potential effects of a single-dose of tracbetedin on the heart's electrical cycle as measured by electrocardiograms (ECGs) in patients with advanced cancer. Participation in the study will include a 21-day screening period, plus two days of single-blinded treatment followed by an optional open-label extension phase. During the single-blind treatment period (1 cycle) patients will sequentially receive trabectedin for 1 day and placebo for 1 day and be monitored for safety for up to 30 days. Only the investigator (physician conducting the study) and study staff will know which treatment the patient receives during the single-blind phase. The open-label phase is optional. The duration of the open-label extension will vary by patient. In this phase, patients will receive trabectedin for as long as the investigator determines that the patient is receiving benefit from the treatment, or until trabectedin becomes commercially available for use, whichever is earlier. There are 2 treatment phases: Single-blind and Open-Label. In the single-blind phase patients will receive one 3-hour intravenous (i.v.) infusion of trabectedin (1.3 mg/m2) on one day and one 3-hour i.v. infusion of trabectedin placebo on another day (treatments will be administered on 2 consecutive days). In the Open-label extension phase, the dose and schedule of trabectedin may modified at the discretion of the Investigator as appropriate depending on the type of malignancy diagnosed.

Inclusion Criteria:

• Patients with locally advanced or metastatic solid tumors who have received three or less prior lines of systemic chemotherapy
• Patients who have relapsed or had progressive disease following standard of care treatment with chemotherapy, or intolerant to prior standard of care treatment with chemotherapy
• Normal cardiac conduction and function as documented on a 12-lead ECG
• Adequate organ function as evidenced by laboratory tests
• Able to receive dexamethasone or its equivalent

Exclusion Criteria:

• Patients treated with more than three prior chemotherapy regimens (including adjuvant therapy)
• Previous exposure to trabectedin
• Central nervous system (CNS) metastasis
• Heart rhythm disturbances, unusual T wave and U wave (if present) morphology, blood pressure outside of normal range, a history of cardiac failure, myocardial infarction, or cardiomyopathy, or a history of additional risk factors for torsade de pointes (e.g. heart failure, electrolyte abnormalities, family history of Long QT Syndrome)
• Patients who at screening are on medication that is known to prolong the QT interval or who are on CYP3A4 inhibitors or inducers