Official Title: “Extended Schedule, Escalated Dose Temozolomide Versus Dacarbazine in Stage IV Metastatic Melanoma: A Randomized Phase III Study of the EORTC Melanoma Group”

The purpose of this study is to ascertain if the extended schedule of Temozolomide, which allows increased doses and potential depletion of the enzyme underlaying resistance, is a more effective treatment of metastatic melanoma than single agent dacarbazine.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2007

Intervention(s) in this Clinical Trial

• Drug: Temozolomide
  • oral capsule; 150 mg/m2/day PO (by mouth), on 7 consecutive days every 14 days ("7 days on / 7 days off" continuously); one cycle of temozolomide is defined as a 6-week period; treatment will continue until progression of the disease, unacceptable toxicity, subject refusal, or opinion of the treating physician that it is in the subject's best interest to stop.
• Drug: Dacarbazine
  • intravenous solution; dacarbazine 1000 mg/m2 IV (in the vein), on Day 1 +/- 3 days every 3 weeks; one cycle of dacarbazine is defined as a 3-week period; treatment will continue until progression of the disease, unacceptable toxicity, subject refusal, or opinion of the treating physician that it is in the subject's best interest to stop.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • temozolomide 150 mg/m2/day PO, on 7 consecutive days every 14 days ("7 days on / 7 days off" continuously)
• Active Comparator: B
  • dacarbazine 1000 mg/m2 IV, on Day 1 +/- 3 days every 3 weeks

Primary Measures

• Overall Survival
  • Time Frame: The final analysis was to be performed when at least 616 deaths had occurred.
    Safety Issue?: No

Secondary Measures

• Progression Free Survival
  • Time Frame: Treatment continued until disease progression or unacceptable toxicity. Patients will be followed for survival.
    Safety Issue?: No
• Objective Response Rate in Subjects With Measurable Lesions
  • Time Frame: Treatment continued until disease progression or unacceptable toxicity.
    Safety Issue?: No
• Duration of Objective Response
  • Time Frame: Treatment continued until disease progression or unacceptable toxicity.
    Safety Issue?: No

Inclusion Criteria:

• Histologically confirmed, stage IV, surgically incurable melanoma
• Age 18 years or older
• WHO (ECOG) performance status of 0 or 1
• Meets protocol requirements for specified laboratory values
• Must be able to take oral medication
• Must be disease free from cancer for period of 5 years (except for surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin).
• Women of childbearing potential and men must be practicing a medically approved contraception.
• Must provide written informed-consent to participate in the study.
• Must have full recovery from major surgery or adjuvant treatment
• No clinically uncontrolled infectious disease including HIV or AIDS-related illness

Exclusion Criteria:

• Ocular melanomas
• Brain Metastases
• Prior cytokine or chemotherapy for stage IV disease
• Pregnant or nursing women

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00091572

Study ID Number: P03267

ClinicalTrials.gov Identifier: NCT00091572

Health Authority: United States: Food and Drug Administration