A Phase II Trial of The Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity
Overview
- Phase
- Phase 2
- Intervention
- Ipilimumab, Melphalan and Dactinomycin
- Conditions
- Melanoma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Progression Free Survival at One Year.
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to see the effect of adding a systemic study drug, Ipilimumab, to two standard chemotherapy drugs, Melphalan and Dactinomycin. The study drug Ipilimumab is an antibody to a normal protein found in the body, CTLA-4. This protein normally allows the immune system (the body's natural defense system that helps fight infections) uses to quiet an immune response. The study drug works by blocking this protein and allowing the immune system to become more active. This study will investigate the effects, of combining ILI (using two standard drugs to treat melanoma, Melphalan and Dactinomycin), with the study drug, Ipilimumab on advanced Melanoma cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to give written informed consent.
- •Histologic diagnosis of melanoma with in transit metastasis Stage IIIB, IIIC, or IV
- •Required values for initial laboratory tests:
- •WBC ≥ 2000/uL
- •ANC ≥ 1000/uL
- •Platelets ≥ 50 x 103/uL
- •Hemoglobin ≥ 8 g/dL
- •Creatinine ≤ 3.0 x ULN
- •AST/ALT ≤ 2.5 x ULN
- •Bilirubin ≤ 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
Exclusion Criteria
- •Any other malignancy form which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
- •Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
- •Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
- •Patients with underlying heart conditions who are deemed ineligible for surgery by cardiology consult
- •Any history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4 inhibitor or agonist.
- •Concomitant therapy with any of the following: IL-2, interferon, or other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids.
- •Women of childbearing potential (WOCBP), who:
- •are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or
- •have a positive pregnancy test at baseline, or
- •are pregnant or breastfeeding.
Arms & Interventions
Ipilimumab, Melphalan and Dactinomycin
This is a single-institution phase II trial with a primary outcome of progression free survival (PFS).
Intervention: Ipilimumab, Melphalan and Dactinomycin
Outcomes
Primary Outcomes
Progression Free Survival at One Year.
Time Frame: 1 year
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Secondary Outcomes
- Toxicity of Additional Ipilimumab Will be Evaluated for All Treated Patients Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0(2 years)
- To Define the Immunologic Events and Signatures at the Tumor Site and in the Periphery That Corresponds to Response to Ipilimumab.(2 years)
- To Determine Response Rates of Combination Therapy. Tumor Assessment Will be Measured by the Immune Related Response Criteria (irRC).(2 years)