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

Primary Purpose

Melanoma

Status
Completed
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Bosentan
Placebo
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Melanoma, Metastatic, DTIC, Bosentan

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Barwon Health - The Geelong Hospital
  • Sydney Haematology and Oncology Unit
  • Cabrini Hopsital - Oncology Department
  • New Castle Melanoma Unit
  • Mount Medical Centre
  • Redcliffe Hospital - Dept Oncology & Palliative Care
  • Mater Adult Hospital
  • Pacific Private Clinic
  • Royal North Shore Hospital
  • Sydney Cancer Centre, Royal Prince Alfred Hospital
  • Westmead Hospital - Department of Oncology
  • Southern Medical Day Care Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Bosentan

Placebo

Arm Description

Outcomes

Primary Outcome Measures

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

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

Full Information

First Posted
October 14, 2009
Last Updated
April 28, 2015
Sponsor
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT01009177
Brief Title
Effect of Bosentan in Patients With Metastatic Melanoma Treated With Dacarbazine (DTIC)
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 Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
February 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Melanoma, Metastatic, DTIC, Bosentan

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bosentan
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Bosentan
Intervention Description
Bosentan 500 mg bid
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
• 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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andjela Kusic-Pajic, MD
Organizational Affiliation
Actelion Pharmaceuticals Australia Pty. Ltd
Official's Role
Study Director
Facility Information:
Facility Name
Barwon Health - The Geelong Hospital
City
Geelong
ZIP/Postal Code
VIC 3220
Country
Australia
Facility Name
Sydney Haematology and Oncology Unit
City
Hornsby
ZIP/Postal Code
NSW
Country
Australia
Facility Name
Cabrini Hopsital - Oncology Department
City
Malvern
ZIP/Postal Code
VIC 2144
Country
Australia
Facility Name
New Castle Melanoma Unit
City
New Castle
ZIP/Postal Code
NSW
Country
Australia
Facility Name
Mount Medical Centre
City
Perth
ZIP/Postal Code
WA
Country
Australia
Facility Name
Redcliffe Hospital - Dept Oncology & Palliative Care
City
Redcliffe
ZIP/Postal Code
QLD 4020
Country
Australia
Facility Name
Mater Adult Hospital
City
South Brisbane
ZIP/Postal Code
QLD 4001
Country
Australia
Facility Name
Pacific Private Clinic
City
Southport
ZIP/Postal Code
QLD 4215
Country
Australia
Facility Name
Royal North Shore Hospital
City
St Leonards
ZIP/Postal Code
NSW
Country
Australia
Facility Name
Sydney Cancer Centre, Royal Prince Alfred Hospital
City
Sydney
ZIP/Postal Code
NSW
Country
Australia
Facility Name
Westmead Hospital - Department of Oncology
City
Westmead
ZIP/Postal Code
NSW 2145
Country
Australia
Facility Name
Southern Medical Day Care Centre
City
Wollongong
ZIP/Postal Code
NSW
Country
Australia

12. IPD Sharing Statement

Citations:
PubMed Identifier
20350333
Citation
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.
Results Reference
derived

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

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