Know Cancer

or
forgot password

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


Phase 2
18 Years
N/A
Not Enrolling
Both
Intraocular Melanoma, Melanoma (Skin)

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome 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

Safety Issue:

Yes

Principal Investigator

Bristol-Myers Squibb

Investigator Role:

Study Director

Investigator Affiliation:

Bristol-Myers Squibb

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000365467

NCT ID:

NCT00084656

Start Date:

May 2004

Completion Date:

Related Keywords:

  • Intraocular Melanoma
  • Melanoma (Skin)
  • 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
  • Melanoma
  • Uveal Neoplasms

Name

Location

H. Lee Moffitt Cancer Center and Research Institute at University of South FloridaTampa, Florida  33612