Temozolomide Versus Dacarbazine in Stage IV Metastatic Melanoma (Study P03267)

Study Overview
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Brief Summary
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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.

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

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Temozolomide
* Drug: Dacarbazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, stage IV, surgically incurable melanoma Age 18 years or older World Health Organization (WHO) Eastern Cooperative Oncology Group (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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>temozolomide 150 mg/m2/day PO, on 7 consecutive days every 14 days (7 days on / 7 days off continuously) | Drug: Temozolomide<br>* 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.<br>* Other names: Temodal, Temodar, SCH 52365;|
| Active Comparator: B<br>dacarbazine 1000 mg/m2 IV, on Day 1 +/- 3 days every 3 weeks | Drug: Dacarbazine<br>* 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.<br>* Other names: DTIC-Dome;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival was defined as the time from the date of randomization to the date of death from any cause. | The final analysis was to be performed when at least 616 deaths had occurred. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival was defined as the time from the date of randomization to the date of disease progression or the date of death regardless of the cause. | Treatment continued until disease progression or unacceptable toxicity. Patients will be followed for survival. | 
| Objective Response Rate in Subjects With Measurable Lesions | Based on investigator's assessment of response in subjects with measurable lesions. Objective response = complete response + partial response. Complete response = disappearance of all target lesions. Partial response = at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter. | Treatment continued until disease progression or unacceptable toxicity. | 
| Duration of Objective Response | Duration of objective response was measured from the time the criteria were met for complete response or partial response to the first date that recurrent or progressive disease was objectively documented. | Treatment continued until disease progression or unacceptable toxicity. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Melanoma