Ipilimumab + Temozolomide in Metastatic Melanoma

Inclusion Criteria

• Patients with histologically documented diagnosis of advanced/inoperable metastatic melanoma of skin or mucosal origin are eligible, provided they fulfill the following conditions:
• They are 18 years old to 75 years old with measurable (at least 1 cm) metastatic disease.
• They have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Must be at least 21 days since surgery, radiation therapy and 6 weeks after immunotherapy with regimens including vaccine, interferon, IL-2 etc. and fully recovered from adverse effects of these therapies.
• Must agree not use vaccines for the treatment of cancer or prevention of disease unless indicated as a component of the protocol regimen (including those for common medical conditions) for up to one month pre and post dosing with ipilimumab.
• Required values for initial laboratory tests: white blood cell count (WBC): 2000/uL or greater, absolute neutrophil count (ANC): 1000/uL or greater, Platelets: 100 x 103/uL or greater, Hemoglobin: 9 g/dL or greater, Creatinine: </=1.5 mg/dL, AST and ALT: </= 2.5 x upper limit of normal (ULN) for subjects without liver metastasis or, </= 5 X upper limit of normal (UNL) for liver metastases, Bilirubin: </= 1.5 mg/dL, LDH </= 2 X upper limit of normal (UNL).
• They have no significant intercurrent illness such as a serious infection which requires intravenous antibiotics. No active or chronic infection with HIV, Hepatitis B, or Hepatitis C. No significant psychiatric illness, which includes any life threatening psychiatric illness that has not been adequately controlled despite intervention (with or without medication) despite 6 months of therapy. They should have no GI tract metastasis or bleeding, no autoimmune disease.
• They have not been previously exposed to any cytotoxic drugs, targeted therapies or anti CTLA 4 drugs for metastatic melanoma. Patients that received interferon for melanoma in the adjuvant setting are eligible. Prior radiation therapy for metastatic melanoma is permitted provided the patient has unirradiated metastatic sites for response evaluation and any toxicity has returned to baseline.
• Patients with brain metastases who have been treated with craniotomy and resection or stereotactic radiosurgery of all symptomatic brain metastases are eligible provided they are 4 weeks from the procedures, MRI/CT of the brain performed within 3 weeks from registration fails to show new metastases and they are off of steroids for at least 2 weeks. Patients previously treated with whole brain radiotherapy are eligible if they are without tumor progression in the brain at least 8 weeks from completion of radiotherapy and are asymptomatic. They should be off steroid therapy for at least 2 weeks.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject.
• (Continued 10) WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as: 1) Amenorrhea 12 consecutive months without another cause, or 2) For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level 35 milli-International unit (mIU)/mL.
• (Continued 11) Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are p