A Phase I Trial of a Vaccine Combining Tyrosinase/GP100/Mart-1 Peptides Emulsified With Montanide ISA 51 With ProGP for Patients With Resected Stages III and IV Melanoma


Phase 1
18 Years
N/A
Not Enrolling
Both
Intraocular Melanoma, Melanoma (Skin)

Thank you

Trial Information

A Phase I Trial of a Vaccine Combining Tyrosinase/GP100/Mart-1 Peptides Emulsified With Montanide ISA 51 With ProGP for Patients With Resected Stages III and IV Melanoma


OBJECTIVES: I. Determine the maximum tolerated dose of filgrastim (G-CSF)-fetal liver
tyrosine kinase-3 (Flt3K) fusion protein when combined with melanoma peptide vaccine
comprising tyrosinase:368-376 peptide, gp100:209-217 antigen, and MART-1:26-35 antigen
emulsified in Montanide ISA-51 in patients with completely resected stage III or IV
melanoma. II. Determine the toxicity and safety of this regimen in these patients. III.
Determine the immune responses to tyrosinase, MART-1, and gp100 antigens in patients before,
during, and after receiving these vaccinations.

OUTLINE: This is a dose escalation, multicenter study of filgrastim (G-CSF)-fetal liver
tyrosine kinase-3 (Flt3K) (G-CSF-Flt3K) fusion protein. Patients receive melanoma peptide
vaccine comprising tyrosinase:368-376 peptide, gp100:209-217 antigen, and MART-1:26-35
antigen emulsified in Montanide ISA-51 subcutaneously (SQ) monthly for 6 months, and then at
9 and 12 months for a total of 8 vaccinations. Patients receive G-CSF-Flt3K fusion protein
SQ daily for 3 days before, immediately after, and then daily for 6 days after each
vaccination. Cohorts of 6-10 patients receive escalating doses of G-CSF-Flt3K fusion protein
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 6-10 patients experience dose limiting toxicity. Patients are
followed every 3 months through year 2 after resection, every 6 months for 3 years, and then
annually thereafter until disease progression.

PROJECTED ACCRUAL: A total of 30-50 patients will be accrued for this study within 12-18
months.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically proven completely resected stage III or IV
cutaneous, mucosal, or ocular melanoma Disease free, but at high risk of relapse Must meet
1 of the following criteria: Failed interferon alfa (IFN-A) therapy Ineligible for IFN-A
therapy Refused IFN-A therapy HLA-A2.1 positive Availability of tumor tissue for analysis
of gp100 antigen staining with antibody HMB-45, and for expression of tyrosinase and
MART-1 antigens by immunohistochemistry Tumor cells must be positive for at least 1
antigen

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0 or 1 Life expectancy:
Not specified Hematopoietic: WBC at least 3,000/mm3 Granulocyte count at least 1,500/mm3
Hemoglobin at least 9.0 g/dL Platelet count at least 100,000/mm3 No coagulation or
bleeding disorders Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT and SGPT no greater
than 2.5 times upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL
Cardiovascular: No concurrent major medical illness of the cardiovascular system
Pulmonary: No concurrent major medical illness of the respiratory system Immunologic:
Hepatitis B surface antigen negative and hepatitis C antibody negative HIV negative No
history of uveitis or other autoimmune inflammatory eye disease No other active autoimmune
disease No known allergic reaction to Montanide ISA-51 Other: No concurrent major systemic
infection including pneumonia or sepsis No concurrent major medical illness of the
gastrointestinal system Not pregnant or nursing Negative pregnancy test No other
malignancy within the past 5 years except curatively treated squamous cell skin cancer or
carcinoma in situ of the cervix allowed 30 days after treatment

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics No prior
tyrosinase:368-376 peptide, gp100:209-217 antigen, or MART-1:26-35 antigen Chemotherapy:
Not specified Endocrine therapy: No concurrent steroids Radiotherapy: At least 1 month
since prior radiotherapy No concurrent radiotherapy Surgery: See Disease Characteristics
Other: At least 1 month since other prior therapy, including adjuvant therapy, for
melanoma No other concurrent anticancer therapy

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Jeffrey S. Weber, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000067857 (10M-99-3)

NCT ID:

NCT00005841

Start Date:

June 2000

Completion Date:

October 2002

Related Keywords:

  • Intraocular Melanoma
  • Melanoma (Skin)
  • iris melanoma
  • ciliary body and choroid melanoma, small size
  • ciliary body and choroid melanoma, medium/large size
  • extraocular extension melanoma
  • recurrent intraocular melanoma
  • stage III melanoma
  • stage IV melanoma
  • recurrent melanoma
  • Melanoma
  • Uveal Neoplasms

Name

Location
USC/Norris Comprehensive Cancer Center Los Angeles, California  90033-0800
City of Hope National Medical Center Los Angeles, California  91010