Phase II Trial of Extended-Dosing Temozolomide in Patients With Melanoma

Study Overview
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Brief Summary
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Temozolomide (also known as TMZ) is a chemotherapy drug given by mouth. It is similar to DTIC, the only FDA-approved chemotherapy for melanoma, but because temozolomide is given by mouth, it can be given daily over a long period of time. We think that temozolomidemay work best if it is given every day for 6 weeks at a time. Temozolomide given by this extended schedule is experimental, although we have found that it is safe and can shrink melanoma in some patients. One big advantage of TMZ is that it is given by mouth instead of by vein. This means that it can be given daily over a long period of time rather than off and on like DTIC. We think that TMZ may work better if it is given every day for 6 weeks. TMZ given by this extended schedule is experimental although we have found that TMZ given in this way is safe and can shrink melanoma in some patients. When extended dosing TMZ was given with either thalidomide or long-acting interferon-α, about 30% of patients had their tumors shrink. We think that this shrinkage was due mostly to the TMZ since neither thalidomide nor interferon-α alpha work in melanoma by themselves. In this study, we will treat patients with TMZ alone using this extended dosing schedule to see how many patients experience tumor shrinkage. We also want to learn more about which tumors are more likely to shrink from TMZ treatment. We will test samples of your tumor for whether or not a gene called MGMT has been turned on,

Official Title
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Phase II Trial of Extended-Dosing Temozolomide in Patients With Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Temozolomide (TMZ)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage III (unresectable) or Stage IV melanoma from a cutaneous or an unknown primary. Histologic proof of melanoma reviewed and confirmed at MSKCC Measurable disease (RECIST criteria) No prior chemotherapy for melanoma. Prior interferon, interleukin-2 or vaccine therapy are allowed. No other concurrent chemotherapy, immunotherapy, or radiotherapy Karnofsky performance status ≥ 60 Adequate organ function defined as follows: ANC > 1500, Platelets > 100,000, creatinine < 2, Alkaline Phosphatase, AST and total bilirubin < 1.5x upper limit of normal. For patients with suspected Gilbert's syndrome bilirubin will not be a requirement. Tumor tissue for MGMT promoter methylation analysis and/or IHC must be available. In most cases, this will be unstained slides from previously-obtained paraffin-embedded tumor material. If this is not available, patients must have an easily-accessable tumor for biopsy (e.g. skin or lymph node). Exclusion Criteria: History of CNS metastases unless brain metastases have been resected and the patient has been free from CNS recurrence for 6 months. Uveal or mucosal melanoma primary Frequent vomiting or medical conditions that could interfere with oral medication intake Serious infection requiring antibiotics, or nonmalignant medical illnesses that are uncontrolled or whose control might be jeopardized by the complications of this therapy. History of HIV infection even if on HAART Immunosuppressive drugs High dose vitamins and herbs Other on-going investigational therapy, concurrent chemotherapy, immunotherapy or radiotherapy.

Ages Eligible for Study
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Minimum Age: 16 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 - Temozolomide (TMZ)<br> | Drug: Temozolomide (TMZ)<br>* One group treatment study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Overall Objective Response Rate (CR and PR). | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | From start of treatment through 24 weeks after ending treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival at 18 months post treatment | 18 months after ending treatment | 
| Duration of Objective Clinical Responses | Duration of Response (Objective Clinical Responses) | 24 weeks after ending treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Memorial Sloan-Kettering Cancer Center patients with measurable, unresectable stage, III or IV melanoma