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

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01009177
• Other study ID #: AC-052-281
• Status: Completed
• Phase: Phase 2
• First received: October 14, 2009
• Last updated: April 28, 2015
• Start date: September 2005
• Est. completion date: February 2008

Study information

• Verified date: April 2015
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• Bosentan
Bosentan 500 mg bid
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Barwon Health - The Geelong Hospital	Geelong
Australia	Sydney Haematology and Oncology Unit	Hornsby
Australia	Cabrini Hopsital - Oncology Department	Malvern
Australia	New Castle Melanoma Unit	New Castle
Australia	Mount Medical Centre	Perth
Australia	Redcliffe Hospital - Dept Oncology & Palliative Care	Redcliffe
Australia	Mater Adult Hospital	South Brisbane
Australia	Pacific Private Clinic	Southport
Australia	Royal North Shore Hospital	St Leonards
Australia	Sydney Cancer Centre, Royal Prince Alfred Hospital	Sydney
Australia	Westmead Hospital - Department of Oncology	Westmead
Australia	Southern Medical Day Care Centre	Wollongong

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to tumor progression (TTP) or death (progression free survival) after initiation of treatment. Tumor progression is defined per RECIST criteria.		6 weekly	No
Secondary	• 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	Yes