A Study of Intra-Patient Escalating Doses of MDX-010 Given Alone or in Combination With Two gp100 Peptides Emulsified With Montanide ISA-51 in the Treatment of Patients With Stage IV Melanoma
16 Years
N/A
Both
Melanoma (Skin)
Trial Information
A Study of Intra-Patient Escalating Doses of MDX-010 Given Alone or in Combination With Two gp100 Peptides Emulsified With Montanide ISA-51 in the Treatment of Patients With Stage IV Melanoma
OBJECTIVES:
Primary
- Determine the clinical response in patients with stage IV melanoma treated with
escalating doses of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal
antibody (MDX-010) with or without gp100 peptides emulsified in Montanide ISA-51.
Secondary
- Determine the safety and toxicity profile of these regimens in these patients.
- Determine the immunologic response in patients treated with these regimens.
- Determine the pharmacokinetics of these regimens in these patients.
- Determine, in HLA-A*0201-positive patients, the differences in responses between
patients previously vaccinated with gp100 peptides and patients not previously
vaccinated.
OUTLINE: This is a 2-part, partially randomized study.
- Part I (closed as of 3/7/2005):
- HLA-A*0201-negative patients: Patients receive anti-cytotoxic
T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes
on day 1. Treatment repeats every 3 weeks for up to 6 doses (3 courses of 3
escalating doses) in the absence of disease progression or unacceptable toxicity.
- HLA-A*0201-positive patients: Patients are stratified according to prior exogenous
gp100 peptide immunization (yes vs no). Patients are randomized to 1 of 2
treatment arms.
- Arm I: Patients receive MDX-010 in the same manner as the HLA-A*0201-negative
patients.
- Arm II: Patients receive MDX-010 as in arm I. Patients also receive
gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51
subcutaneously immediately after each MDX-010 infusion.
- Part II:
- HLA-A*0201-negative patients (closed as of 3/7/2005): Patients receive MDX-010 as
in part I. Treatment repeats every 3 weeks for up to 4 doses (2 courses of 2
escalating doses, beginning with a higher dose level than in part I) in the
absence of disease progression or unacceptable toxicity.
- HLA-A*0201-positive patients: Patients are stratified and randomized as in part I.
- Arm I: Patients receive MDX-010 in the same manner as the HLA-A*0201-negative
patients.
- Arm II: Patients receive MDX-010 as in arm I. Patients also receive
gp100:209-217 and gp100:280-288 peptides emulsified in Montanide ISA-51
subcutaneously immediately after each MDX-010 infusion.
In both parts, patients with stable disease or a complete response (CR) after completing all
courses of MDX-010 may receive 1 additional course of therapy in the absence of unacceptable
toxicity. Patients achieving a partial response may continue to recieve treatment with
MDX-010 at the same dose, in the absence of unacceptable toxicity, until CR or until tumor
is no longer shrinking.
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 35-179 patients (up to 35 for part I [closed as of 3/7/05] and
69-141 [23-47 per arm (arm I closed as of 3/7/05)] for part II) will be accrued for this
study within 3-4 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed stage IV melanoma
- Clinically evaluable or measurable disease
- No mucosal or ocular melanoma
PATIENT CHARACTERISTICS:
Age
- 16 and over
Performance status
- ECOG 0-2
Life expectancy
- At least 6 months
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9 g/dL
- Hematocrit ≥ 28%
- WBC ≥ 2,500/mm^3
Hepatic
- AST ≤ 3 times upper limit of normal (ULN)
- Bilirubin ≤ ULN (< 3 mg/dL for patients with Gilbert's syndrome)
- Hepatitis B surface antigen negative
- Hepatitis C virus antibody negative
Renal
- Creatinine < 2 mg/dL
Immunologic
- HIV negative
- No history of any of the following:
- Inflammatory bowel disease
- Regional enteritis
- Connective tissue disorders (e.g., systemic lupus erythematosus)
- Rheumatoid arthritis
- Autoimmune inflammatory eye disease
- Sjögren's syndrome
- Inflammatory neurologic disorder (e.g., multiple sclerosis)
- No active infection
- No active autoimmune disease that may cause life-threatening symptoms or severe
organ/tissue damage
- Vitiligo, autoimmune thyroiditis, or skin rashes associated with prior therapy
are allowed if patient has recovered to grade 1 or less toxicity
- No systemic hypersensitivity to study agents
- Prior local reaction (e.g., delayed hypersensitivity or glaucomatous reactions)
to Montanide ISA-51 or gp100 injections allowed
- No autoimmune disease requiring active therapy with any form of steroid or
immunosuppressant
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No concurrent underlying medical condition that would preclude study participation
- 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
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
- Prior therapy with gp100 peptides or any other immunotherapy allowed
Chemotherapy
- At least 6 weeks since prior nitrosoureas and recovered (toxicity no greater than
grade 1)
- No concurrent chemotherapy
Endocrine therapy
- At least 4 weeks since prior steroids
- No concurrent systemic, inhaled, optical, or topical corticosteroids
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- At least 3 weeks since prior systemic therapy for melanoma and recovered (toxicity no
greater than grade 1)
- No concurrent immunosuppressive agents (e.g., cyclosporine)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Outcome Measure:
Objective response (partial and complete)
Safety Issue:
No
Principal Investigator
Steven A. Rosenberg, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
NCI - Surgery Branch
Authority:
United States: Federal Government
Study ID:
040083
NCT ID:
NCT00077532
Start Date:
March 2004
Completion Date:
February 2008
Related Keywords:
- Melanoma (Skin)
- stage IV melanoma
- recurrent melanoma
- Melanoma
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
