Inclusion Criteria:

1. Male or female patients 18 years of age or older

2. Histologically proven malignant melanoma (Balch et al., J. Clin Oncol. 19(16):
3635-48, 2001) with stage IV measurable disease as defined by RECIST criteria
(Therasse et al., J Natl Cancer Inst, 92(3): 205-16, 2000).

3. Patients with prior radiation therapy (> 30 days prior to study drug initiation) will
be allowed provided the indicator lesion(s) used for this study was (were) outside
the field of radiation or represent new lesions not previously irradiated.

4. Patients who had no prior therapy with DTIC.

5. Patients with cutaneous melanoma lesions must consent to having a biopsy obtained
during the screening period and at the end of treatment for exploratory analysis of
endothelin receptor expression. Biopsies obtained prior to the study that have been
frozen in accordance with procedures specified for this protocol may be used.

6. ECOG performance status (≤ 2)

7. Life expectancy > 12 weeks

8. Female patients must be non-pregnant, non-breast feeding, and either post menopausal,
surgically sterile, or practicing a reliable method of contraception (hormonal
methods alone are not sufficient)

9. Provide written informed consent

10. Willing to return to study center for follow up

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