Clinical trial NCT00084656: Monoclonal Antibody Therapy and Vaccine Therapy in Treating Patients With Resected Stage III or Stage IV Melanoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intraocular Melanoma
Melanoma (Skin)
Keywords: 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
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-11
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: 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

Primary outcomes:
measure: Percentage of Participants With Immune-related Adverse Events (irAEs)
timeFrame: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
measure: Time to Disease Relapse
timeFrame: up to 3 years
Secondary outcomes:
measure: Number of Participants With Drug-related irAEs of Any Grade
timeFrame: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
measure: Immunologic Response to the Dose Regimen
timeFrame: up to 3 years
measure: Number of Participants Experiencing Hematology-related Lab Abnormalities
timeFrame: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
measure: Number of Participants Experiencing Serum Chemistry-related Lab Abnormalities
timeFrame: Between first dose and 70 days after last dose of study therapy (up to 3 years including maintenance phase)
measure: Time to Disease Relapse
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Garg SK, Ott MJ, Mostofa AGM, Chen Z, Chen YA, Kroeger J, Cao B, Mailloux AW, Agrawal A, Schaible BJ, Sarnaik A, Weber JS, Berglund AE, Mule JJ, Markowitz J. Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy. Front Immunol. 2020 Feb 25;11:164. doi: 10.3389/fimmu.2020.00164. eCollection 2020.
citation: Sarnaik AA, Yu B, Yu D, Morelli D, Hall M, Bogle D, Yan L, Targan S, Solomon J, Nichol G, Yellin M, Weber JS. Extended dose ipilimumab with a peptide vaccine: immune correlates associated with clinical benefit in patients with resected high-risk stage IIIc/IV melanoma. Clin Cancer Res. 2011 Feb 15;17(4):896-906. doi: 10.1158/1078-0432.CCR-10-2463. Epub 2010 Nov 24.