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

Sponsor

Craig L Slingluff, Jr (Other)

Overall Status

Completed

CT.gov ID

NCT00118313

Collaborator

National Cancer Institute (NCI) (NIH)

Location

20.7

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	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	Phase 1

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 4, 2004

Actual Primary Completion Date :

Jul 28, 2006

Actual Study Completion Date :

Jul 28, 2006

Outcome Measures

Primary Outcome Measures

Safety if less than 33% of patients experience a dose-limiting at day 22 []

Secondary Outcome Measures

Immune response by Elispot assay at day 22 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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