Monoclonal Antibody Therapy and Vaccine Therapy in Treating Patients With Resected Stage III or Stage IV Melanoma
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Purpose
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Vaccines may make the body build an immune response to kill tumor cells. Combining the vaccines with Montanide ISA-51 may cause a stronger immune response and kill more tumor cells. Giving monoclonal antibody therapy together with vaccine therapy may be an effective treatment for stage III or stage IV melanoma.
PURPOSE: This phase II trial is studying how well giving monoclonal antibody therapy together with vaccine therapy works in treating patients with resected stage III or stage IV melanoma.
| Condition | Intervention | Phase |
|---|---|---|
|
Intraocular Melanoma Melanoma (Skin) |
Biological: ipilimumab Biological: Tyrosinase/gp100/MART-1 Peptides |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | An Extended Dosing, Two-phase Study of MDX-010 as Monotherapy or in Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 VG in the Treatment of Subjects With Resected Stage III or Stage IV Melanoma |
- First part of study: To achieve at least a 40% immune-related adverse event rate defined by the induction of Grade 1, grade 2, or acceptable grade 3 drug-related immune-related adverse events [ Time Frame: Weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, 47, 53, then every 3 months for up to two additional years ] [ Designated as safety issue: Yes ]
- Second part of study: To determine the time to disease relapse and to determine the rate of acceptable immune-related Grade 1, grade 2, or acceptable grade 3 drug-related immune-related adverse events [ Time Frame: Weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, 47, 53, then every 3 months for up to two additional years ] [ Designated as safety issue: Yes ]
- Determine incidence of drug-related irAEs (1st & 2nd part) through clinical and laboratory assessment of immune-related adverse events [ Time Frame: 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, 47, 53, then every 3 months for up to two additional years ] [ Designated as safety issue: Yes ]
- Determine time to disease relapse (1st part) through diagnostic imaging assessments, including brain MRI [ Time Frame: Approximately every 3 months] ] [ Designated as safety issue: No ]
- Determine immunologic response (1st & 2nd part) through assay of peripheral blood samples [ Time Frame: Weeks 1, 9, 11, 17, 21, 25, 33, 41, and 53 ] [ Designated as safety issue: Yes ]
- Evaluate toxicity profile (1st & 2nd part) through clinical and laboratory assessment of adverse events [ Time Frame: Weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, 47, 53, then every 3 months for up to two additional years ] [ Designated as safety issue: Yes ]
| Enrollment: | 75 |
| Study Start Date: | May 2004 |
| Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Arm 1 |
Biological: ipilimumab
IV over 90 mins on day 1, wks 1,9,17,25,33,41,53 Dose: 3 mg/kg (Part I), 10 mg/kg (Part II)
Biological: Tyrosinase/gp100/MART-1 Peptides
(All subjects in Part I and HLA-A*0201 positive subjects only in Part II): SC, day 1 of wks 1,3,5,7,9,11,17, 21,25,33,41,53 Dose: 1 mg peptide emulsified in 1 mL Montanide ISA 51 VG.)
|
Detailed Description:
OBJECTIVES:
Primary
- Achieve at least a 40% autoimmune breakthrough event rate, as defined by the induction of grade 1, grade 2, or acceptable grade 3 drug-related autoimmune adverse events, in patients with resected stage III or IV melanoma treated with anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51.
Secondary
- Determine the incidence of drug-related autoimmune adverse events of any grade in patients treated with this regimen.
- Determine the time to disease relapse in patients treated with this regimen.
- Determine the immunologic response in patients treated with this regimen.
OUTLINE: This is an open-label study.
Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1 of weeks 1, 9, 17, 25, 33, 41, and 53 and peptide vaccine comprising tyrosinase, gp100 antigen, and MART-1 antigen emulsified in Montanide ISA-51 subcutaneously on day 1 of weeks 1, 3, 5, 7, 9, 11, 17, 21, 25, 33, 41, and 53.
Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed melanoma
- Stage III (≥ 3 positive lymph nodes) or stage IV disease
- Mucosal or ocular melanoma allowed
- Completely resected within the past 6 months
- Patients with stage III resected melanoma rendered free of disease may have failed, been ineligible for, or refused prior treatment with interferon alfa
Positive staining of tumor tissue for at least one of the following:
- Antibody HMB-45 for gp100
- Antibody HMB-45 for tyrosinase
- Antibody HMB-45 for MART-1
- HLA-A*0201 positive by DNA allele-specific polymerase chain reaction assay
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- At least 6 months
Hematopoietic
- WBC ≥ 2,500/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hematocrit ≥ 30%
- Hemoglobin ≥ 10 g/dL
Hepatic
- AST ≤ 3 times upper limit of normal (ULN)*
- Bilirubin ≤ ULN* (< 3.0 mg/dL for patients with Gilbert's syndrome)
- No significant hepatic disease that would preclude study participation
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative NOTE: * Unless attributable to disease
Renal
- Creatinine ≤ 2.0 mg/dL
- No significant renal disease that would preclude study participation
Cardiovascular
- No significant cardiac disease that would preclude study participation
Pulmonary
- No significant pulmonary disease that would preclude study participation
Immunologic
No history of any of the following:
- Inflammatory bowel disease or any other autoimmune bowel disease
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Autoimmune ocular disease
- No systemic hypersensitivity to Montanide ISA-51 or any vaccine component
- No active infection requiring therapy
- HIV negative
Other
- 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 significant gastrointestinal disease that would preclude study participation
- No significant psychiatric disease that would preclude study participation
- No other medical condition that would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 4 months after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010)
- No prior gp100 antigen, MART-1 antigen, or tyrosinase peptide
- At least 4 weeks since prior immunotherapy for melanoma and recovered
- No other concurrent immunotherapy
Chemotherapy
- At least 4 weeks since prior chemotherapy for melanoma (6 weeks for nitrosoureas) and recovered
- No concurrent chemotherapy
Endocrine therapy
- At least 4 weeks since prior hormonal therapy for melanoma and recovered
- At least 4 weeks since prior systemic, inhaled, or topical corticosteroids
- No concurrent systemic, inhaled, or topical corticosteroids
Radiotherapy
- At least 4 weeks since prior radiotherapy for melanoma and recovered
Surgery
- See Disease Characteristics
- At least 4 weeks since prior surgery for melanoma and recovered
Other
- No concurrent immunosuppressive agents (e.g., cyclosporine and its analog)
- Concurrent analgesic therapy allowed provided the dose is stable for the past 14 days
Contacts and Locations| United States, Florida | |
| H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | |
| Tampa, Florida, United States, 33612-9497 | |
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided by Bristol-Myers Squibb
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Study Director, Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT00084656 History of Changes |
| Other Study ID Numbers: | CDR0000365467, P30CA076292, P30CA014089, MCC-15241, MDX010-16, NCI-6446, CA184-016 |
| Study First Received: | June 10, 2004 |
| Last Updated: | April 23, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Bristol-Myers Squibb:
|
stage III melanoma stage IV melanoma ciliary body and choroid melanoma, medium/large size extraocular extension melanoma |
iris melanoma recurrent melanoma recurrent intraocular melanoma metastatic intraocular melanoma |
Additional relevant MeSH terms:
|
Melanoma Uveal Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms |
Neoplasms, Nerve Tissue Nevi and Melanomas Eye Neoplasms Neoplasms by Site Eye Diseases Uveal Diseases |
ClinicalTrials.gov processed this record on June 13, 2013