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

Sponsor

Actelion (Industry)

Overall Status

Completed

CT.gov ID

NCT01009177

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

6.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Bosentan Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Feb 1, 2008

Actual Study Completion Date :

Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bosentan	Drug: Bosentan Bosentan 500 mg bid
Placebo Comparator: Placebo	Drug: Placebo Placebo

Arm

Intervention/Treatment

Experimental: Bosentan

Drug: Bosentan

Bosentan 500 mg bid

Placebo Comparator: Placebo

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Time to tumor progression (TTP) or death (progression free survival) after initiation of treatment. Tumor progression is defined per RECIST criteria. [6 weekly]

Secondary Outcome Measures

• 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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)
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.
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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Barwon Health - The Geelong Hospital	Geelong	Australia	VIC 3220
2	Sydney Haematology and Oncology Unit	Hornsby	Australia	NSW
3	Cabrini Hopsital - Oncology Department	Malvern	Australia	VIC 2144
4	New Castle Melanoma Unit	New Castle	Australia	NSW
5	Mount Medical Centre	Perth	Australia	WA
6	Redcliffe Hospital - Dept Oncology & Palliative Care	Redcliffe	Australia	QLD 4020
7	Mater Adult Hospital	South Brisbane	Australia	QLD 4001
8	Pacific Private Clinic	Southport	Australia	QLD 4215
9	Royal North Shore Hospital	St Leonards	Australia	NSW
10	Sydney Cancer Centre, Royal Prince Alfred Hospital	Sydney	Australia	NSW
11	Westmead Hospital - Department of Oncology	Westmead	Australia	NSW 2145
12	Southern Medical Day Care Centre	Wollongong	Australia	NSW