Official Title: “Evaluation of the Impact of Adjuvants Accompanying Peptide Immunization in High Risk Melanoma”

RATIONALE: Vaccines made from gp100 peptides may help the body build an effective immune response to kill tumor cells. Substances like Montanide ISA-51 and imiquimod help stimulate the immune system. Giving the vaccine together with Montanide ISA-51 and/or imiquimod after surgery may make a stronger immune response to kill any remaining tumor cells and prevent or delay the recurrence of melanoma.

PURPOSE: This randomized phase II trial is studying how well vaccine therapy works together with or without Montanide ISA 51 and/or imiquimod in treating patients with melanoma that has been removed by surgery.

Study Type: Interventional

Study Design: Treatment, Randomized

Study Primary Completion Date: September 2006

OBJECTIVES: - Evaluate the immunologic activity of immunization with 4 different preparations of the gp100:209-217(210M) melanoma antigen peptide (comprising montanide ISA-51 VG and/or imiquimod) and potentially select one for further study in patients with resected high-risk melanoma.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 6 treatment arms (treatment arms I-IV closed to accrual as of 1/11/08). - Arm I (closed to accrual as of 1/11/08): Patients receive immunization with gp100:209-217(210M) peptide emulsified in Montanide ISA-51 VG subcutaneously on day 1. - Arm II (closed to accrual as of 1/11/08): Patients receive immunization as in arm I (closed to accrual as of 1/11/08). After injection, patients also apply imiquimod at the site of injection once daily on days 1-5. - Arm III (closed to accrual as of 1/11/08): Patients receive immunization with gp100:209-217(210M) peptide mixed in sodium chloride intradermally on day 1. - Arm IV (closed to accrual as of 1/11/08): Patients receive immunization as in arm III (closed to accrual as of 1/11/08). After injection, patients apply imiquimod at the site of injection once daily on days 1-5. - Arm V: Patients receive immunization with gp100:209-217(210M) peptide emulsified using a 3-way stopcock with 2 syringes in Montanide ISA-51 VG subcutaneously on day 1. - Arm VI: Patients receive immunization as in arm V. After injection, patients apply imiquimod at the site of once daily on days 1-5.

In all arms, treatment repeats every 21 days for 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for 1 year and then annually for 5 years.

PROJECTED ACCRUAL: A total of 145 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: gp100 antigen
  • Given subcutaneously
• Drug: imiquimod
  • Applied at the site of injection
• Drug: incomplete Freund's adjuvant
  • Given subcutaneously

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I (closed to accrual as of 1/11/08)
  • Patients receive immunization with gp100:209-217(210M) peptide emulsified in Montanide ISA-51 VG subcutaneously on day 1.
• Experimental: Arm II (closed to accrual as of 1/11/08)
  • Patients receive immunization as in arm I (closed to accrual as of 1/11/08). After injection, patients also apply imiquimod at the site of injection once daily on days 1-5.
• Experimental: Arm III (closed to accrual as of 1/11/08)
  • Patients receive immunization with gp100:209-217(210M) peptide mixed in sodium chloride intradermally on day 1.
• Experimental: Arm IV (closed to accrual as of 1/11/08)
  • Patients receive immunization as in arm III (closed to accrual as of 1/11/08). After injection, patients apply imiquimod at the site of injection once daily on days 1-5.
• Experimental: Arm V
  • Patients receive immunization with gp100:209-217(210M) peptide emulsified using a 3-way stopcock with 2 syringes in Montanide ISA-51 VG subcutaneously on day 1.
• Experimental: Arm VI
  • Patients receive immunization as in arm V. After injection, patients apply imiquimod at the site of once daily on days 1-5.

Primary Measures

• Immunologic activity
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Diagnosis of primary melanoma meeting any of the following criteria:
• Ulcerated lesions ≥ 2 mm
• Any lesion ≥ 4.0 mm in thickness
• At least 1 positive lymph node
• Local recurrence
• Metastatic disease
• Disease surgically resected within the past 6 months
• Clinically disease free by radiography within 6 weeks prior to study entry
• HLA-A* 0201 positive
• No ocular or mucosal melanoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0 or 1
• Creatinine ≤ 2.0 mg/dL
• Bilirubin ≤ 1.6 mg/dL (3.0 mg/dL for Gilbert's syndrome)
• WBC ≥ 3,000/mm^3
• Platelet count ≥ 90,000/mm^3
• AST/ALT < 3 times normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active systemic infections, autoimmune disease (e.g., autoimmune colitis or Crohn's disease), or any known immunodeficiency disease
• No known positivity for hepatitis B surface antigen or HIV antibody
• No known hypersensitivity to any agents used in this study

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 3 weeks since prior systemic anticancer therapy, including adjuvant immunotherapy (e.g., interferon)
• Recovered from prior therapy (vitiligo or alopecia allowed)
• Recovered immune competence after prior radiotherapy
• No prior immunization with gp100 antigen
• No prior chemotherapy for treatment of melanoma
• No concurrent systemic steroid therapy
• No other concurrent systemic anticancer therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

Steven A. Rosenberg, MD, PhD Study Chair NCI - Surgery Branch  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00304057

Study ID Number: CDR0000465410

ClinicalTrials.gov Identifier: NCT00304057

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database

Web site for additional information