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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate the Effect of Bosentan in Patients With Stage IV Metastatic Melanoma Treated With Dacarbazine

Phase 2
18 Years
70 Years
Not Enrolling

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Trial Information

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate the Effect of Bosentan in Patients With Stage IV Metastatic Melanoma Treated With Dacarbazine

This is a randomized, double-blind (1:1 bosentan : placebo) trial to evaluate the effect of
bosentan in combination with DTIC on TTP or death in patients with metastatic melanoma stage

The patients will receive study medication (bosentan or placebo) and DTIC for 35 weeks to
105 weeks; the study will be completed when 66 events (tumor progression, death due to
underlying disease, other/additional anti-tumor therapy) have been observed.

Study drug will be administered orally, 500 mg twice a day. DTIC will be given once every
three weeks in a dosage of 1000 mg/m2 intravenously (i.v.) or in accordance with the
Institution's DTIC treatment protocol.

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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Time to tumor progression (TTP) or death (progression free survival) after initiation of treatment. Tumor progression is defined per RECIST criteria.

Outcome Time Frame:

6 weekly

Safety Issue:


Principal Investigator

Andjela Kusic-Pajic, MD

Investigator Role:

Study Director

Investigator Affiliation:

Actelion Pharmaceuticals Australia Pty. Ltd


Australia: Human Research Ethics Committee

Study ID:




Start Date:

September 2005

Completion Date:

February 2008

Related Keywords:

  • Melanoma
  • Melanoma
  • Metastatic
  • DTIC
  • Bosentan
  • Melanoma