Ipilimumab + Temozolomide in Metastatic Melanoma
Condition: Metastatic Melanoma
MeSH terms: Melanoma
Intervention: Ipilimumab; Temozolomide
Intervention description: Induction Phase: 10 mg/kg by vein (IV) over approximately 90 minutes on Day 1 only repeated every 3 weeks until 4 courses of therapy are given over 3 months. For the Maintenance Phase, dose repeated every 12 weeks.; Induction Phase, 200 mg/m^2 by mouth (PO) on Days 1 to 4, repeated every 3 weeks until 4 courses of therapy are given over 3 months. For the Maintenance Phase, dose delivered on Days 1 to 5, repeated every 4 weeks.
Intervention MeSH terms: Temozolomide; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Advanced; Inoperable; Melanoma; Ipilimumab; MDX010; BMS-734016; Temozolomide; Temodar; TMZ; skin; mucosal

Summary:

      The goal of this clinical research study is to learn if combining ipilimumab and temozolomide
      can help to control metastatic melanoma. The safety of this drug combination will be studied.
      Researchers would also like to study how this therapy affects the levels of certain chemicals
      in the blood that are related to your immune system.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histologically documented diagnosis of advanced/inoperable metastatic
             melanoma of skin or mucosal origin are eligible, provided they fulfill the following
             conditions:

          2. They are 18 years old to 75 years old with measurable (at least 1 cm) metastatic
             disease.

          3. They have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          4. 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.

          5. 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.

          6. 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).

          7. 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.

          8. 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.

          9. 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.

         10. 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.

         11. (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.

         12. (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 practicing abstinence or where their partner
             is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP
             must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or
             equivalent units of HCG) within 72 hours before the start of ipilimumab.

         13. Men should use condoms while participating in this study.

         14. must agree not to 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 of ipilimumab.

        Exclusion Criteria:

          1. Patients with Uveal melanoma. Patients with skin or mucosal melanoma who are younger
             than 18 years or more than 75 years of age and those with an ECOG performance status
             of 2, 3 or 4, or patients without measurable metastases.

          2. Patients with prior cytotoxic, targeted therapy or anti-CTLA 4 drugs for metastatic
             disease.

          3. Patients with significant cardiac illness such as symptomatic coronary artery disease
             or previous history of myocardial infarction, impaired left ventricle function or
             serious cardiac arrhythmias requiring therapy. Borderline cases must be discussed with
             the PI.

          4. Patients with significant impairment of pulmonary function on account of chronic
             bronchitis or chronic obstructive pulmonary disease (COPD). Pulmonary function test
             with the results forced expiratory volume at one second (FEV1) <65% or forced vital
             capacity (FVC) <65% of predicted. Borderline cases must be discussed with the PI.

          5. Patients on corticosteroids or any other type of immunosuppressive agent (e.g.,
             methotrexate, chloroquine, azathioprine, cyclophosphamide) at time of enrollment only.

          6. Patients with history of second malignancies such as basal cell carcinoma, squamous
             cell carcinoma and carcinoma in situ of cervix are eligible for therapy. Patients with
             history of other types of cancers, are eligible provided that they have been free of
             recurrence from second malignancy for at least 3 years. Each case must be discussed
             with the PI prior to registration.

          7. Patients with symptomatic uncontrolled brain metastasis that is associated with
             significant brain edema requiring steroid therapy. Patients will be evaluated by the
             principal investigator or his designee. Patients with spinal cord metastasis or
             meningeal carcinomatosis.

          8. WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid
             pregnancy. Acceptable contraceptive methods are using oral contraceptives, other
             hormonal contraceptives (vaginal products, skin patches, implanted or injectable
             products), or mechanical products such as an intrauterine device or barrier methods
             (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence
             or where their partner is sterile (eg, vasectomy).