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

NCT00580060 | Completed Early Phase 1

• 2 other identifiers: 00-142NCI Protocol #: 5906
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot trial to investigate the use of GM-CSF DNA as an adjuvant for peptide vaccination in patients with metastatic melanoma. The objective of this study is to determine the safety and adjuvant effect of vaccination with the gene coding for human GM-CSF with a multi-epitope melanoma peptide vaccine (tyrosinase and gp100 peptides) in patients with AJCC stage IIB, IIC, III and IV melanoma who are HLA-A2+. We will assess whether use of GM-CSF DNA is safe and generates an immune response to peptides derived from antigens on melanoma cells.

Conditions

Melanoma

Keywords

AJCC; stage; IIB; IIC; III; IV; Melanoma; HLA-A2+; Vaccine

Outcome Measures

Primary Outcomes (4)

• To establish the safety and a recommended dose of subcutaneous human GM-CSF DNA given in conjunction with a multi-epitope peptide vaccine in patients with AJCC stage IIB, IIC, III and IV melanoma who are HLA-A2+.

  Up to 15 years post treatment,

• To evaluate serum pharmacokinetics of GM-CSF after subcutaneous administration of human GM-CSF DNA.

  All patients entered in the Dose Ranging study will undergo pharmacokinetic studies during their first course of therapy.

• If toxicities are encountered in the dose ranging part of the study, to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).

  If toxicities less than DLT are encountered, then patients will continue on the study at the assigned dose level.

• In the immunological efficacy study, to evaluate the immunogenicity of a multi-epitope peptide vaccine.

  Up to 15 years post treatment.

Secondary Outcomes (1)

• A secondary endpoint is to observe the patients for evidence of any anti-tumor response that is generated after vaccination.

  Up to 15 years post treatment

Interventions

GM-CSF DNA, NSC 683472 gp100: 209-217(210M), NSC 699048 Tyrosinase: 368-376(370D) BIOLOGICAL

In the Dose Ranging part of the study, cohorts of 3 patients will be treated at increasing dose levels of GM-CSF DNA delivered subcutaneously (100, 400, or 800 mg), followed by administration of both peptides subcutaneously to the same site on day 5 or day 6. Patients will be treated monthly for three immunizations.

Also known as: GM-CSF DNA, NSC 683472 gp100: 209-217(210M), NSC 699048 Tyrosinase: 368-376(370D)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have documented malignant melanoma, American Joint Commission on Cancer (AJCC) stage IIB, IIC, III or IV (54). Patients with resectable stage IIB, IIC and III disease must have undergone surgical resection before participating in this study.
• Patients with choroidal melanoma may participate if they fulfill one of the following criteria: Basal diameter \> or = 16 mm; Height \> or = 8 mm or involvement of ciliary body with tumor.
• For all patients, pathology slides must be reviewed by the Pathology Department of Memorial Sloan-Kettering Cancer Center for confirmation of melanoma diagnosis.
• Patients must be HLA-A2 positive.
• Patients must weigh at least 25 kg to be eligible. Patients must be able to read the consent form and give informed consent. Parent or legal guardians of patients who are minors will sign the informed consent form.
• Patients must have a Karnofsky performance status of at least 80.
• LDH ≤ 2x upper limit of normal value; albumin ≥ 3.5 mg/dl. Creatinine ≤ 2mg/dl and AST ≤ 2- fold upper limit of normal.
• A CBC prior to vaccination with WBC ≥ 3000, platelets ≥ 100,000.
• A negative serum bHCG within 2 weeks of vaccination in women of childbearing age.
• Patients must be free of detectable brain metastases. (Brain MRI or CT pre-protocol)

You may not qualify if:

• Patients may not be receiving or have received chemotherapy, immunotherapy or radiation therapy within the previous 4 weeks or nitrosourea chemotherapy within the previous 6 weeks. Patients must be fully recovered from any previous therapy or surgery.
• Patients may not have been previously immunized with vaccines containing tyrosinase or gp100, or peptides derived from tyrosinase or gp100.
• Creatinine \> 2mg/dl (or history of Creatinine \> 2 mg/dl) and AST ≥ 2 fold upper limit of normal.
• Patients who have preexisting retinal or choroidal eye disease (except as outlined in section 5.1.1) will be excluded.
• Patients with serious underlying medical conditions, active infections requiring antimicrobial drugs, or active bleeding will be ineligible.
• Pregnant women, women who are less than 3 months post-partum or women who are nursing are not eligible. Women of childbearing age and sexually active men must be using appropriate contraception during the course of this study and for 3 months following completion.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Miguel-Angel Perales, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 24, 2007
• Study Start: December 1, 2003
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: June 10, 2011

Record last verified: 2011-06

Locations

US (1)