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

NCT ID: NCT01009177

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2008-02-29

Brief Summary

The study is designed as a multicenter, double blind, parallel-group, placebo-controlled, randomized, event driven Phase II study of DTIC with or without bosentan as first-line treatment in patients with stage IV melanoma.

Detailed Description

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 IV.

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.

Conditions

Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Bosentan

Group Type: EXPERIMENTAL

Bosentan

Intervention Type: DRUG

Bosentan 500 mg bid

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Bosentan

Bosentan 500 mg bid

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andjela Kusic-Pajic, MD

Role: STUDY_DIRECTOR

Actelion Pharmaceuticals Australia Pty. Ltd

References

Kefford RF, Clingan PR, Brady B, Ballmer A, Morganti A, Hersey P. A randomized, double-blind, placebo-controlled study of high-dose bosentan in patients with stage IV metastatic melanoma receiving first-line dacarbazine chemotherapy. Mol Cancer. 2010 Mar 30;9:69. doi: 10.1186/1476-4598-9-69.

Reference Type: DERIVED

PMID: 20350333 (View on PubMed)

Other Identifiers

AC-052-281

Identifier Type: -

Identifier Source: org_study_id