Temozolomide Alone or With Pegylated Interferon-Alpha 2b (PGI) in Melanoma Patients
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Temozolomide (TMZ); Pegylated Interferon Alpha-2b (PGI)
Intervention description: 150 mg/m^2 by mouth once daily for 7 days, followed by 7 days off (alternating weekly) for a total of 8 weeks.; 0.5 mcg/kg subcutaneous injection once weekly for a total of 8 weeks.
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Melanoma; Temozolomide; Temodar; Pegylated Interferon Alpha-2b; PEG-Intron; PGI; Resectable metastatic melanoma; Surgery

Summary:

      The goal of this clinical research study is to learn if temozolomide alone or given with
      pegylated interferon alpha-2b can help to control metastatic melanoma. Researchers also want
      to study the safety of these 2 treatments.

      Objectives:

        1. To determine the anti-tumor activity (pathological response CR+PR) and toxicity of
           temozolomide (TMZ) alone or in combination with pegylated interferon alpha-2b (PGI) in
           patients with resectable stage IIIC or stage IV (M1a) metastatic melanoma prior to
           definitive surgical resection.

        2. To determine the relapse-free survival, overall survival and the impact of tumor
           response to chemotherapy in these patients.

        3. To differentiate the in vivo treatment effects of TMZ alone vs.TMZ plus PGI and
           correlate with clinical outcome by analysis the pre- and post-treatment tumors and
           peripheral blood mononuclear cells with respect to:

      1) Known cellular and molecular markers of apoptosis and cell proliferation, 2) Promotor
      methylation status of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), 3)
      DNA sequence variability of tumor suppressor genes and DNA repair enzymes, 4) Tumor genomic
      expression profiles analysis by complementary DNA (cDNA) microarray and protein array
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically documented diagnosis of melanoma metastases.

          2. Stage IIIB/IIIC (N2b, N2c and N3) or stage IV (M1a) melanoma patients with measurable
             and potentially resectable metastases without clinical and radiological evidence of
             other distant metastases.

          3. An Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          4. Age 18 or older.

          5. Adequate organ function defined as follows: a.) Absolute granulocytes greater than or
             equal to 1,000/mm^3 and Platelets greater than or equal to 100,000/mm^3, b.) Serum
             bilirubin and serum creatinine of less than or equal to 1.5 times upper limit of
             laboratory normal. If serum creatinine is greater than 1.5 times upper limit of
             laboratory normal, the urine creatinine clearance must be greater than 60 ml/min., c.)
             serum glutamate oxaloacetate transaminase (SGOT) (AST), serum glutamate pyruvate
             transaminase (SGPT) (ALT) and alkaline phosphatase less than or equal to 3 times upper
             limit of laboratory normal.

          6. Patients have not had any previous systemic chemotherapy for metastatic melanoma.
             Prior biologic therapy, targeted therapy or immunotherapy are allowable, but must be
             at least 2 weeks since prior therapy before starting study drugs. No other concurrent
             chemotherapy, immunotherapy, or radiotherapy.

          7. Prior radiation therapy used to enhance local regional control is permitted, but must
             be at least 2 weeks since prior therapy before starting study drugs. In addition, the
             patient must have unirradiated metastatic sites for response evaluation and has fully
             recovered from its toxicity. Lesions within the prior field of radiation may only be
             used as indicator lesions if there has been recent evidence of disease progression
             after .

          8. Ability to understand and sign an informed consent form, indicating awareness of the
             investigational nature of this study.

        Exclusion Criteria:

          1. Significant cardiac or pulmonary dysfunction, such as a history of severe
             cardiovascular disease, myocardial infarction within 6 months of the start of
             treatment, unstable angina, Class III or Class IV congestive heart failure,
             ventricular arrhythmia, or any uncontrolled arrhythmia.

          2. Current significant psychiatric illness.

          3. Serious infection requiring intravenous antibiotics, or any non-malignant medical
             illnesses that are uncontrolled or whose control may be jeopardized by complications
             of this therapy.

          4. Frequent vomiting or any medical condition (e.g. partial bowel obstruction) that could
             interfere with oral medication intake.

          5. Autoimmune or immunosuppressive disorders (e.g. HIV or AIDS-related illness).

          6. Patients who require therapy with systemic corticosteroids.

          7. No evidence of active secondary malignancy that requires chemotherapy within the past
             2 years (excluding non-melanoma skin cancer, and/or all carcinoma in-situ)

          8. Pregnant or lactating women are ineligible. Women of childbearing potential must have
             a negative urine pregnancy test within a week of initiation of therapy. All patients
             must agree to use medically approved contraceptive measures to prevent pregnancy
             during treatment.

          9. Any other medical condition or reason that, in the principal investigator's opinion,
             makes the patient unsuitable to participate in a clinical trial.