Effect of Bosentan in Patients With Metastatic Melanoma Treated With Dacarbazine (DTIC)

Exclusion Criteria

• •1. ALT and/or AST \> 3 × the upper limit of normal (ULN) at screening OR ALT and /or AST \> 2 x ULN and total bilirubin \> 2.0 mg/dl at screening
• •2. Lactate dehydrogenase \> 1.5 x ULN
• •3. Hemoglobin \>30% below the lower limit of normal
• •4. Systolic blood pressure \< 85 mmHg
• •5. NYHA class III/IV congestive heart failure
• •6. Any prior chemotherapy, biological therapy or immunotherapy for stage IV metastatic disease.
• •7. Received immunotherapy \< 30 days before treatment start (completed adjuvant immunotherapy for previous resected metastatic disease is allowed)
• •8. Concurrent use of calcineurin inhibitors (cyclosporine A, tacrolimus), sirolimus, fluconazole or glibenclamide (glyburide) or expected to receive any of these drugs during the study at inclusion and during the study.
• •9. History of other malignancy in the last 5 years, with the exception of squamous cell carcinoma of the skin treated with local resection and basal cell carcinoma
• •10. CNS metastases or carcinomatous meningitis
• •11. Ocular melanoma
• •12. Known hypersensitivity to any excipients of Tracleer™
• •13. Prior therapy with bosentan
• •14. Use of therapy with another investigational drug within 4 weeks of the start of dosing with bosentan or plan to receive such treatment during the study
• •15. Known drug or alcohol dependence or any other factor that will interfere with the conduct of the study
• •16. Any standard contraindications for the use of DTIC as per Australian package insert