Vaccine Therapy With or Without Imiquimod in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Biological therapies, such as imiquimod, may stimulate the immune system in different ways and stop tumor cells from growing. Giving vaccine therapy together with imiquimod after surgery may help the body kill any remaining tumor cells. PURPOSE: This randomized phase I trial is studying the side effects and best way to give vaccine therapy with or without imiquimod in treating patients who have undergone surgery for stage II, stage III, or stage IV melanoma.

Detailed Description
-----------------
OBJECTIVES: Determine the safety of adjuvant transdermal vaccine therapy comprising multi-epitope melanoma peptides (MP), tetanus toxoid helper peptide (TET), and sargramostim (GM-CSF) in combination with Montanide ISA-51 or dimethyl sulfoxide with or without imiquimod in patients who have undergone surgical resection for stage II-IV melanoma. Determine, preliminarily, the immunogenicity of these regimens in these patients. Correlate, preliminarily, transdermal administration of these vaccines with the recruitment and maturation of epidermal Langerhans cells in these patients. Determine, preliminarily, the effects of timing of subsequent vaccine therapy comprising MP, TET, and GM-CSF emulsified in Montanide ISA-51, administered intradermally and subcutaneously, on the persistence of immune response in these patients. OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 4 treatment arms. Arm I: Patients receive vaccine therapy comprising multi-epitope melanoma peptides (MP), tetanus toxoid helper peptide (TET), and sargramostim (GM-CSF) emulsified in Montanide ISA-51 transdermally (TD) on days 1, 8, and 15. Patients then receive the vaccine intradermally (ID) and subcutaneously (SC) on days 29, 50, 71, 92, 113, and 134. Arm II: Patients receive vaccine therapy as in arm I. Patients also receive imiquimod topically on days 0, 7, and 14. Arm III: Patients receive vaccine therapy comprising MP, TET, GM-CSF, and dimethyl sulfoxide TD on days 1, 8, and 15. Patients then receive vaccine therapy comprising MP, TET, and GM-CSF emulsified in Montanide ISA-51 ID and SC on days 29, 50, 71, 92, 113, and 134. Arm IV: Patients receive vaccine therapy as in arm III and imiquimod as in arm II. In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 3 and 5 weeks and then at disease progression. PROJECTED ACCRUAL: A maximum of 26 patients (approximately 6 per treatment arm) will be accrued for this study within approximately 2 years.

Official Title
-----------------
Evaluation of Different Adjuvants for the Transdermal Administration of a Peptide-Based Vaccine in Participants With High-Risk Melanoma

Conditions
-----------------
Melanoma (Skin)

Intervention / Treatment
-----------------
* Biological: incomplete Freund's adjuvant
* Biological: multi-epitope melanoma peptide vaccine
* Biological: sargramostim
* Biological: tetanus toxoid helper peptide
* Drug: dimethyl sulfoxide
* Drug: imiquimod
* Procedure: adjuvant therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed melanoma Stage II-IV disease Has undergone surgical resection within the past 12 months No clinical or radiological evidence of disease after surgical resection Must have ≥ 1 undissected axillary and/or inguinal lymph node basin HLA-A1, -A2, or -A3 positive Ineligible for OR refused interferon PATIENT CHARACTERISTICS: Age 12 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count > 1,000/mm^3 Platelet count > 100,000/mm^3 Hemoglobin > 9 g/dL Hepatic AST and ALT ≤ 2.5 times upper limit of normal (ULN) Bilirubin ≤ 2.5 times ULN Lactic dehydrogenase ≤ 1.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Hepatitis C negative Renal Creatinine ≤ 1.5 times ULN Cardiovascular No New York Heart Association class III or IV heart disease Immunologic HIV negative No known or suspected allergy to any component of the study vaccines No autoimmune disorder with visceral involvement No prior active autoimmune disorder requiring cytotoxic or immunosuppressive therapy The following immunologic conditions are allowed: Laboratory evidence of autoimmune disease (e.g., positive anti-nuclear antibody titer) without symptoms Clinical evidence of vitiligo Other forms of depigmenting illness Mild arthritis requiring non-steroidal anti-inflammatory drugs Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Weight ≥ 110 lbs No uncontrolled diabetes Hemoglobin A1C < 7% (for patients with diabetes) No medical contraindication or potential problem that would preclude study compliance No known active addiction to alcohol or drugs No recent (within the past year) or ongoing illicit IV drug use PRIOR CONCURRENT THERAPY: Biologic therapy Prior vaccinations that resulted in recurrent disease during or after vaccine administration allowed provided the last vaccination was administered more than 12 weeks ago Prior multi-epitope melanoma peptide vaccine that resulted in a negative immune response allowed More than 4 weeks since prior and no concurrent interferon (e.g., Intron-A®), interleukins (e.g., Proleukin®), or growth factors (e.g., Procrit®, Aranesp®, or Neulasta®) More than 4 weeks since prior and no concurrent allergy desensitization injections No influenza vaccine for at least 2 weeks before or after study vaccine administration Chemotherapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas [e.g., carmustine or lomustine]) No concurrent chemotherapy, including nitrosoureas Endocrine therapy More than 4 weeks since prior and no concurrent oral or parenteral corticosteroids (e.g., prednisone) No prior or concurrent inhaled steroids (e.g., Advair®, Flovent®, Azmacort®) Concurrent topical corticosteroids allowed Radiotherapy More than 4 weeks since prior and no concurrent radiotherapy Prior stereotactic radiosurgery allowed provided it was completed within the past 12 months Surgery See Disease Characteristics More than 4 weeks since prior surgical resection of metastatic lesion(s) No concurrent surgery requiring general anesthesia Other More than 4 weeks since prior and no other concurrent investigational agents More than 30 days since prior and no concurrent participation in another clinical study No other concurrent immunosuppressive therapy

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: incomplete Freund's adjuvant|nan|
|Biological: multi-epitope melanoma peptide vaccine|nan|
|Biological: sargramostim|nan|
|Biological: tetanus toxoid helper peptide|nan|
|Drug: dimethyl sulfoxide|nan|
|Drug: imiquimod|nan|
|Procedure: adjuvant therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety if less than 33% of patients experience a dose-limiting at day 22 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response by Elispot assay at day 22 |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage II melanoma, stage III melanoma, stage IV melanoma