Phase II Trial of Neoadjuvant Temozolomide in Melanoma Patients With Palpable Stage III or IV Disease Undergoing Complete Surgical Resection
Condition: Melanoma; Skin Cancer; Cancer
MeSH terms: Melanoma; Skin Neoplasms
Intervention: Temozolomide
Intervention description: At the start of the trial a core needle biopsy of a palpable tumor will be obtained percutaneously in the office after administration of local anesthesia. Patients will then be treated with TMZ according to the extended dosing schedule of 75mg/m2/day x 6 weeks every 8 weeks. After each cycle, patients will be re-evaluated for response.
Responding patients will be offered another cycle of treatment. Patients will be treated until best response, progression of disease, or 6 cycles, whichever comes first.
After completing temozolomide treatment, patients will be evaluated for surgical resection. It is expected that, unless there is progression of disease, patients will undergo resection (i.e. therapeutic lymph node dissection). In patients who have a complete clinical response to temozolomide, whether or not to do a subsequent lymph node dissection will be left up to the discretion of the surgeon and the patient.
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Melanoma; Skin Cancer; Cancer; Temozolamide; TMZ

Summary:

      In this study, we want to find out how likely it is for temozolomide to shrink melanoma
      tumors that have spread only to areas that could be removed by surgery. We also want to study
      the melanoma before and after temozolomide treatment to learn why some tumors respond and
      others do not. This is a Phase II trial. This means that it will test a drug - in this case,
      temozolomide -- that has already been studied and shown to be safe.

      Surgery, when possible, is the main treatment for patients with melanoma like yours. In most
      people, however, melanoma cells have already spread to other places in the body. This means
      that even with surgery, many people will have the melanoma come back. This is often fatal.

      One goal of this trial is to treat the melanoma cells that might have spread before they have
      a chance to grow.

      As part of this trial, we also study which genes are turned on and which genes are turned off
      in your tumor. We will obtain tumor from the biopsy done before you started temozolomide
      treatment and from the tumor removed during the surgery done after you finish temozolomide
      treatment. This may help us understand how temozolomide works and how to recognize which
      tumors will respond.

      Before and during the temozolomide treatment, we will also test a new way of measuring the
      amount of tumor present. This involves a special way of analyzing the CT scan which you will
      have anyway. This new technique may allow us to see tumor shrinkage very early in the
      treatment course.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Palpable Stage III (N1b, N2b, N2c, or N3) or Stage IV (M1a) cutaneous melanoma.
             Patient must be a potential candidate for complete surgical resection.

          -  Age ≥ 18 years

          -  Histologic proof of pathology reviewed and confirmed at MSKCC

          -  Measurable disease by RECIST criteria

          -  Determination of surgical resectability by surgeon at MSKCC

          -  No prior chemotherapy for melanoma. Prior interferon, interleukin-2 or vaccine therapy
             is allowed.

          -  No other concurrent chemotherapy, immunotherapy, or radiotherapy

          -  Karnofsky performance status ≥60

          -  Adequate organ function

        Exclusion Criteria:

          -  Uveal or mucosal melanoma

          -  Patients with melanoma deemed not amenable to surgical resection or who are not
             surgical candidates for medical reasons

          -  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

          -  Pregnancy or nursing

          -  History of HIV infection even if on HAART as TMZ leads to CD4+ T cell leukopenia

          -  Concurrent use of high dose vitamins and herbs

          -  Other on-going investigational therapy, concurrent chemotherapy, immunotherapy or
             radiotherapy