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

NCT01009177 | Completed Phase 2 DMC

• 1 other identifier: AC-052-281
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Melanoma

Keywords

Melanoma; Metastatic; DTIC; Bosentan

Outcome Measures

Primary Outcomes (1)

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

  6 weekly

Secondary Outcomes (1)

• • Tumor response rate • Duration of overall response • Best overall response • Survival will be assessed at 12 months after initiation of study drug and every year thereafter for 5 years

  6 weekly

Study Arms (2)

Bosentan

EXPERIMENTAL

Drug: Bosentan

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Bosentan DRUG

Bosentan 500 mg bid

Bosentan

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18 years of age or older
• 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).
• 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.
• Patients who had no prior therapy with DTIC.
• 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.
• ECOG performance status (≤ 2)
• Life expectancy \> 12 weeks
• 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)
• Provide written informed consent
• Willing to return to study center for follow up

You may not qualify if:

• 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
• Lactate dehydrogenase \> 1.5 x ULN
• Hemoglobin \>30% below the lower limit of normal
• Systolic blood pressure \< 85 mmHg
• NYHA class III/IV congestive heart failure
• Any prior chemotherapy, biological therapy or immunotherapy for stage IV metastatic disease.
• Received immunotherapy \< 30 days before treatment start (completed adjuvant immunotherapy for previous resected metastatic disease is allowed)
• 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
• CNS metastases or carcinomatous meningitis
• Ocular melanoma
• Known hypersensitivity to any excipients of Tracleer™
• Prior therapy with bosentan
• 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
• Known drug or alcohol dependence or any other factor that will interfere with the conduct of the study
• Any standard contraindications for the use of DTIC as per Australian package insert

Sponsors & Collaborators

• Actelion: lead

Related Publications (1)

• 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.

  PMID: 20350333 DERIVED

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Andjela Kusic-Pajic, MD

  Actelion Pharmaceuticals Australia Pty. Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2009
• First Posted: November 6, 2009
• Study Start: September 1, 2005
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: February 3, 2025

Record last verified: 2025-01