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

This study has been completed.
Sponsor:
Information provided by:
Actelion
ClinicalTrials.gov Identifier:
NCT01009177
First received: October 14, 2009
Last updated: July 20, 2010
Last verified: July 2010
  Purpose

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 Intervention Phase
Melanoma
Drug: Bosentan
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Time to tumor progression (TTP) or death (progression free survival) after initiation of treatment. Tumor progression is defined per RECIST criteria. [ Time Frame: 6 weekly ] [ Designated as safety issue: No ]

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 [ Time Frame: 6 weekly ] [ Designated as safety issue: Yes ]

Enrollment: 80
Study Start Date: September 2005
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bosentan Drug: Bosentan
Bosentan 500 mg bid
Placebo Comparator: Placebo Drug: Placebo
Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01009177

Locations
Australia
Barwon Health - The Geelong Hospital
Geelong, Australia, VIC 3220
Sydney Haematology and Oncology Unit
Hornsby, Australia, NSW
Cabrini Hopsital - Oncology Department
Malvern, Australia, VIC 2144
New Castle Melanoma Unit
New Castle, Australia, NSW
Mount Medical Centre
Perth, Australia, WA
Redcliffe Hospital - Dept Oncology & Palliative Care
Redcliffe, Australia, QLD 4020
Mater Adult Hospital
South Brisbane, Australia, QLD 4001
Pacific Private Clinic
Southport, Australia, QLD 4215
Royal North Shore Hospital
St Leonards, Australia, NSW
Sydney Cancer Centre, Royal Prince Alfred Hospital
Sydney, Australia, NSW
Westmead Hospital - Department of Oncology
Westmead, Australia, NSW 2145
Southern Medical Day Care Centre
Wollongong, Australia, NSW
Sponsors and Collaborators
Actelion
Investigators
Study Director: Andjela Kusic-Pajic, MD Actelion Pharmaceuticals Australia Pty. Ltd
  More Information

No publications provided by Actelion

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Andrea Ballmer/Clinical Trial Leader, Actelion Pharmaceuticals Ltd
ClinicalTrials.gov Identifier: NCT01009177     History of Changes
Other Study ID Numbers: AC-052-281
Study First Received: October 14, 2009
Last Updated: July 20, 2010
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by Actelion:
Melanoma
Metastatic
DTIC
Bosentan

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014