Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy With Immune Adjuvant in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Melanoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed Any age (weight > 25 kg) NCI MSKCC-00142A 5906, NCI-5906, NCT00085137

Objectives

Primary

1. Determine the maximum tolerated dose and recommended dose of sargramostim (GM-CSF) plasmid DNA adjuvant with a multi-epitope peptide vaccine comprising tyrosinase peptide and gp100 antigen in patients with stage IIB, IIC, III, or IV melanoma who are HLA-A2-positive.
2. Determine the safety of this regimen in these patients.
3. Determine the pharmacokinetics of this regimen in these patients.
4. Determine the dose-limiting toxic effects of this regimen in these patients.
5. Determine the immunogenicity of this regimen in these patients.

Secondary

1. Determine any anti-tumor response in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignant melanoma
  • Stage IIB, IIC, III, or IV disease



• Patients with resectable disease must have undergone surgical resection before study entry
  • Patients free of disease after surgical resection are eligible up to 6 months after resection



• HLA-A0201 positive



• No detectable brain metastases by brain MRI or CT scan

Prior/Concurrent Therapy:

Biologic therapy

• More than 4 weeks since prior immunotherapy
• No prior vaccines containing tyrosinase peptide or gp100 antigen or peptides derived from tyrosinase peptide or gp100 antigen
• No other concurrent immunotherapy

Chemotherapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
• No concurrent chemotherapy

Endocrine therapy

• More than 6 weeks since prior systemic corticosteroids
  • Inhaled or nasal steroids allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• Recovered from all prior therapy
• No concurrent medication that would preclude study participation

Patient Characteristics:

Age

• Any age if weight > 25 kg (55 lb)

Performance status

• Karnofsky 80-100%

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm³
• Platelet count ≥ 100,000/mm³
• No active bleeding

Hepatic

• Lactic dehydrogenase ≤ 2 times upper limit of normal (ULN)
• Albumin ≥ 3.5 mg/dL
• AST ≤ 2 times ULN

Renal

• Creatinine ≤ 2 mg/dL
• No prior creatinine > 2 mg/dL

Other

• Must weigh ≥ 25 kg
• No medical condition that would preclude study participation (e.g., active autoimmune disease or immunodeficiency)
• No pre-existing retinal or choroidal eye disease
• No inflammation of the eyes
• No serious underlying medical conditions
• No active infection requiring antimicrobial drugs
• Not pregnant or nursing
  • At least 3 months post-partum
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study participation

Expected Enrollment

A total of 3-27 patients (3-18 for phase I and 9 for phase II) will be accrued for this study within 2-14 months.

Outcomes

Immunological efficacy in terms of T-cell response as measured by enzyme-linked immunospot

Outline

This is a phase I, pilot, dose-escalation study of sargramostim (GM-CSF) plasmid DNA adjuvant followed by a phase II, pilot study.

• Phase I: Patients receive GM-CSF plasmid DNA adjuvant subcutaneously (SC) on day 1 and a vaccine comprising tyrosinase peptide and gp100 antigen SC on day 5. Treatment repeats every 28 days for a total of 3 courses in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of GM-CSF plasmid DNA adjuvant until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.




• Phase II: Patients receive vaccination as in phase I at the MTD.

Patients are followed at least once annually for at least 15 years.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Miguel-Angel Perales, MD, Principal investigator		Ph: 212-639-8682; 800-525-2225
Paul Chapman, MD, Principal investigator		Ph: 646-888-2378; 800-525-2225
Alan Houghton, MD, Principal investigator		Ph: 212-639-7595; 800-525-2225
Jedd Wolchok, MD, Principal investigator		Ph: 646-888-2395; 800-525-2225

Registry Information
Official Title		Injection Of AJCC Stage IIB, IIC, III And IV Melanoma Patients With A Multi-Epitope Peptide Vaccine Using GM-CSF DNA As An Adjuvant: A Pilot Trial To Assess Safety And Immunity
Trial Start Date		2003-12-30
Registered in ClinicalTrials.gov		NCT00085137 1
Date Submitted to PDQ		2004-04-16
Information Last Verified		2006-08-15
NCI Grant/Contract Number		CA33049, CA08748

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00085137