Phase II Trial of Extended-Dosing Temozolomide in Patients With Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Temozolomide (TMZ)
Intervention description: One group treatment study
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Memorial Sloan-Kettering Cancer Center patients with measurable, unresectable stage; III or IV melanoma

Summary:

      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,
    

Eligibility criteria:

        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.