Intraocular Melanoma, Melanoma (Skin)
Conditions
Keywords
stage IV melanoma, extraocular extension melanoma, recurrent melanoma, iris melanoma, ciliary body and choroid melanoma, medium/large size, ciliary body and choroid melanoma, small size, recurrent intraocular melanoma
Brief summary
RATIONALE: Biological therapies, such as MDX-010, work in different ways to stimulate the immune system and stop tumor cells from growing. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Combining monoclonal antibody therapy with interleukin-2 may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combining monoclonal antibody therapy with interleukin-2 in treating patients who have metastatic melanoma.
Detailed description
OBJECTIVES: * Determine the maximum tolerated dose (MTD) of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) in combination with high-dose interleukin-2 (IL-2) in patients with metastatic melanoma. (Phase I is closed to accrual as of 4/13/2004). * Determine the activity of MDX-CTLA4 administered at the MTD with high-dose IL-2 in these patients. * Determine whether the administration of IL-2 alters the pharmacokinetics of MDX-CTLA4 in these patients. * Determine the safety and adverse event profile of this regimen in these patients. OUTLINE: This is an open-label, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4). * Phase I: Patients receive MDX-CTLA4 IV on days 0, 21, and 42. Patients also receive high-dose interleukin-2 (IL-2) IV over 15 minutes every 8 hours for up to 15 doses beginning on days 22 and 43. Treatment repeats every 63 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with an ongoing partial response and no greater than grade 1 toxicity may receive additional courses of therapy. Patients who require discontinuation of MDX-CTLA4 due to toxicity may continue receiving IL-2 at the discretion of the investigator. Cohorts of 3-6 patients receive escalating doses of MDX-CTLA4 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. (Phase I is closed to accrual as of 4/13/2004). * Phase II: Patients receive treatment as in phase I at the MTD of MDX-CTLA4. Patients who achieve a partial or complete response and later develop recurrent or progressive disease may be retreated at the same dose. Patients are followed at 3 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 3-51 patients (3-18 for phase I and 19-33 for phase II) will be accrued for this study within 1 year. (Phase I is closed to accrual as of 4/13/2004).
Interventions
BIOLOGICALaldesleukin
BIOLOGICALipilimumab
Sponsors
National Cancer Institute (NCI)
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed stage IV melanoma * Mucosal or ocular melanoma also eligible * Clinically evaluable disease * At least 1 site of measurable disease PATIENT CHARACTERISTICS: Age * 16 and over Performance status * ECOG 0-1 Life expectancy * At least 3 months Hematopoietic * WBC at least 2,500/mm\^3 * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Hemoglobin at least 10 g/dL * Hematocrit at least 30% Hepatic * Bilirubin no greater than upper limit of normal (ULN)\* (less than 3.0 mg/dL in patients with Gilbert's syndrome) * AST no greater than 3 times ULN\* * Hepatitis B surface antigen negative * Hepatitis C antibody nonreactive * No evidence or history of significant hepatic disease that would preclude safe administration of high-dose IL-2 NOTE: \*Unless attributable to disease Renal * Creatinine no greater than 2.0 mg/dL * No evidence or history of significant renal disease that would preclude safe administration of high-dose IL-2 Cardiovascular * No evidence or history of significant cardiac disease that would preclude safe administration of high-dose IL-2 * Thallium stress test normal (for patients over 50 years of age or with a history of cardiovascular disease) Pulmonary * No evidence or history of significant pulmonary disease that would preclude safe administration of high-dose IL-2 Immunologic * HIV negative * No autoimmune disease (including uveitis and autoimmune inflammatory eye disease) * No active infection Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix * No evidence or history of significant gastrointestinal disease that would preclude safe administration of high-dose IL-2 * No evidence or history of psychiatric disease that would preclude safe administration of high-dose IL-2 * No other underlying medical condition that would make the administration of the study drug hazardous or obscure the interpretation of adverse events * No other concurrent medical condition that would preclude study entry PRIOR CONCURRENT THERAPY: Biologic therapy * At least 3 weeks since prior immunotherapy for melanoma and recovered * No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) * No prior high-dose (at least 600,000 IU/kg every 8 hours) interleukin-2 (IL-2) Chemotherapy * At least 3 weeks since prior chemotherapy for melanoma and recovered * No concurrent chemotherapy Endocrine therapy * At least 3 weeks since prior hormonal therapy for melanoma and recovered * At least 4 weeks since prior corticosteroids * No concurrent systemic or topical corticosteroids Radiotherapy * At least 3 weeks since prior radiotherapy for melanoma and recovered Surgery * Not specified Other * No concurrent immunosuppressive agents (e.g., cyclosporine or its analog)
Countries
United States
Outcome results
None listed