Clinical trial NCT00028431: Novel Adjuvants for Peptide-Based Melanoma Vaccines
Official title: An Open Label Study of MDX-CTLA4 in Combination With Tyrosinase/gp100/MART-1 Peptides Emulsified With Montanide ISA 51 in the Treatment of Patients With Resected Stage III or IV Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: Stage III melanoma
Stage IV melanoma
Interleukin-12
Cancer Vaccines
Antineoplastic Agents, Combined
Incomplete Freund's adjuvant
Monophenol Monooxygenase
Mannitol
Adjuvants, Immunologic
Melan-A Protein
Antigens, Neoplasm
Antibodies
Melanocyte lineage-specific antigen gp100
CTLA-4
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2002-01-09
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study to determine the efficacy of a melanoma vaccine chemotherapy cocktail composed of CTLA-4 antibody; tyrosinase, gp100, and MART-1 peptides; and incomplete Freund's adjuvant (IFA) with or without interleukin-12 in patients with resected stage III or IV melanoma.

Detailed description: In the Phase I/II trial, patients with resected stages III and IV melanoma who have been rendered free of disease, but are at high risk of relapse, are treated with peptides/IFA at a dose of 0.5 mg each peptide plus CTLA-4 antibody given intravenously, 3 mg/kg, after each vaccination. In the Phase II randomized study, patients are treated with the melanoma peptide vaccine alone, with CTLA-4 antibody, or with CTLA-4 antibody combined with IL-12 at 30 ng/kg with alum. The peptides are tyrosinase 368-376 (370D); gp100 209-217 (210M); and MART-1 26-35 (27L) which are emulsified with IFA. The dosing schedule for both trials are at 1, 2, 3, 4, 5, and 6 months; then at 9 and 12 for a total of 8 vaccinations.

Eligibility criteria: Inclusion criteria:

* Diagnosis of stage III or IV cutaneous, mucosal, or ocular melanoma
* Completely resected disease or disease-free
* HLA-A2.1 positive
* Tumor tissue available for immunohistochemical analysis and staining positive for at least 1 of the specified antigens
* At least 1 month since prior therapy for cancer, including radiotherapy and adjuvant therapy
* WBC count at least 3,000/mm3
* Granulocyte count at least 1,500/mm3
* Platelet count at least 100,000/mm3
* Hemoglobin at least 9.0 gm/dL
* Creatinine no greater than 2.0 mg/dL
* Bilirubin no greater than 2.0 mg/dL
* SGOT/SGPT no greater than 2.5 times upper limit of normal
* ECOG performance status 0-1
* Have failed alpha-interferons (patients with resected stage III disease)

Exclusion criteria:

* Prior treatment with tyrosinase: 368-376(370D), gp100:209-217(210M), and MART-1:26-35(27L) peptides
* Steroid therapy or other immunosuppressive medication requirement
* Major systemic infections (e.g., pneumonia or sepsis)
* Coagulation or bleeding disorders
* Major medical illnesses of the gastrointestinal, cardiovascular, or respiratory systems
* Allergic reaction to Montanide ISA 51 (incomplete Freund's adjuvant)
* History of uveitis or autoimmune inflammatory eye disease
* Other active autoimmune disease
* Positive for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody
* Pregnant or nursing

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Universtiy of Southern California/Kenneth Norris, Jr. Comprehensive Cancer Center
state: California
Study officials:
affiliation: University of Southern California/Norris Cancer Center
name: Jeffrey S. Weber, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: