Clinical trial NCT01009177 (phase 2, status: completed)
Conditions: melanoma
ICD codes: C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4
Drugs: bosentan, placebo
SMILES: COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        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