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.
Interventional
Allocation: Randomized, Primary Purpose: Treatment
Objective response (partial and complete)
No
Steven A. Rosenberg, MD, PhD
Principal Investigator
NCI - Surgery Branch
United States: Federal Government
040083
NCT00077532
March 2004
February 2008
Name | Location |
---|---|
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |