Vaccine Therapy Using Melanoma Peptides for Cytotoxic T Cells and Helper T Cells in Treating Patients With Metastatic Melanoma - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00071981

Purpose

RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells.

PURPOSE: This randomized phase II trial is studying four different vaccines using melanoma peptides from cytotoxic T cells and helper T cells to see how well they work in treating patients with metastatic melanoma.

Condition	Intervention	Phase
Melanoma (Skin)	Biological: incomplete Freund's adjuvant Biological: melanoma helper peptide vaccine Biological: multi-epitope melanoma peptide vaccine Biological: sargramostim Biological: tetanus peptide melanoma vaccine	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Randomized Phase II Trial of Multi-Epitope Vaccination With Melanoma Peptides For Cytotoxic T Cells And Helper T Cells For Patients With Metastatic Melanoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Sargramostim Freund's adjuvant

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Immune response as measured by amount of peripheral blood T-cell lymphocytes present over the first 6 weeks [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical response as measured by amount of helper T-cells present at week 8 [ Designated as safety issue: No ]

Estimated Enrollment:	169
Study Start Date:	March 2005
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.	Biological: incomplete Freund's adjuvant Given by injection Biological: multi-epitope melanoma peptide vaccine Given by injection Biological: sargramostim Given by injection
Arm II: Experimental Patients receive 2 injections of multi-epitope peptide vaccine comprising 12MP and 1 tetanus helper peptide emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.	Biological: incomplete Freund's adjuvant Given by injection Biological: multi-epitope melanoma peptide vaccine Given by injection Biological: sargramostim Given by injection Biological: tetanus peptide melanoma vaccine Given by injection
Arm III: Experimental Patients receive 2 injections of multi-epitope peptide vaccine comprising 12MP and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.	Biological: incomplete Freund's adjuvant Given by injection Biological: melanoma helper peptide vaccine Given by injection Biological: multi-epitope melanoma peptide vaccine Given by injection Biological: sargramostim Given by injection
Arm IV: Experimental Patients receive 2 injections of multi-epitope peptide vaccine comprising 6HP emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.	Biological: incomplete Freund's adjuvant Given by injection Biological: melanoma helper peptide vaccine Given by injection Biological: sargramostim Given by injection

Detailed Description:

OBJECTIVES:

Compare the cytotoxic T-cell response to each of 12 melanoma peptides restricted by HLA-A1, -A2, or -A3 in patients with metastatic melanoma vaccinated with or without these 12 melanoma peptides and with or without helper peptides.
Compare the helper T-cell response to each of 6 melanoma helper peptides restricted by HLA-DR molecules in patients treated with these vaccinations.
Determine whether the addition of 6 melanoma helper peptides to a vaccine containing multiple class I MHC-restricted peptides augments T-cell responses to the class I restricted peptides in these patients.
Determine, preliminarily, whether booster vaccination maintains immune response in patients treated with these vaccinations.
Compare the rates of clinical response and survival in patients treated with these vaccinations.
Determine, preliminarily, whether cellular immune response correlates with clinical response and survival rates in patients treated with these vaccinations.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to HLA type (HLA-A1 vs HLA-A2 vs HLA-A1 and -A2 vs HLA-A3) and planned sentinel immunized node biopsy (yes vs no). Patients are randomized to 1 of 4 treatment arms.

Arm I: Patients receive 2 injections of multi-epitope peptide vaccine comprising 12 melanoma peptides restricted by Class I MHC (12MP) emulsified with sargramostim (GM-CSF) and Montanide ISA-51 or Montanide ISA-51 VG (ISA-51) intradermally (ID) and subcutaneously (SC) on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.
Arm II: Patients receive 2 injections of multi-epitope peptide vaccine comprising 12MP and 1 tetanus helper peptide emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.
Arm III (closed to accrual as of 5/19/08): Patients receive 2 injections of multi-epitope peptide vaccine comprising 12MP and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.
Arm IV: Patients receive 2 injections of multi-epitope peptide vaccine comprising 6HP emulsified with GM-CSF and ISA-51 ID and SC on day 1 of weeks 1-3 and 1 injection at the primary site only on day 1 of weeks 5-7.

In all arms, patients continue therapy in the absence of unacceptable toxicity or disease progression necessitating other urgent therapy.

Patients are evaluated at 8 and 12 weeks. Beginning 2-3 weeks after the week-12 evaluation, patients with no evidence of disease progression may receive booster vaccinations according to their randomized treatment arm. Patients receive booster vaccination ID and SC once weekly for 3 weeks. Treatment repeats every 9 weeks for 1 course, every 12 weeks for 2 courses, and then every 24 weeks for 2 courses OR for up to 2 years (whichever comes first) provided the patient does not require an urgent change in therapy.

After completion of study treatment, patients are followed every 6 months for 2 years and then for survival for 5 years from study randomization.

PROJECTED ACCRUAL: A total of 176 patients (44 per treatment arm) will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed stage IV melanoma
- Multiple primary melanomas allowed
- Metastasis may be from a cutaneous, mucosal, ocular, or unknown primary site
Measurable disease by RECIST criteria
Must have 2 extremities uninvolved with tumor
Must have at least 2 intact (undissected) axillary and/or inguinal lymph node basins
- Prior sentinel node biopsy may not have violated the integrity of a nodal basin
  - This extremity may still be considered for vaccination
HLA-A1, -A2, or -A3 positive
Prior brain metastases allowed provided all of the following are true:
- No more than 3 brain metastases
- Metastatic lesions no greater than 2 cm
- Surgically resected or treated with gamma-knife or stereotactic radiosurgery
- No disease progression in the brain for the past 3 months
- More than 30 days since prior steroids for the management of brain metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-1

Life expectancy

Not specified

Hematopoietic

WBC at least 4,000/mm^3
Platelet count at least 100,000/mm^3
Lymphocyte count at least 700/mm^3

Hepatic

SGOT and SGPT no greater than 2 times upper limit of normal (ULN)
Bilirubin no greater than 2 times ULN
Alkaline phosphatase no greater than 2 times ULN
Lactic dehydrogenase no greater than 2 times ULN

Renal

Creatinine no greater than 1.8 mg/dL

Immunologic

No known or suspected major allergy to any components of the study vaccine
No significant detectable infection
No immunosuppression conditions
No prior or active autoimmune disorder requiring cytotoxic or immunosuppressive therapy, except for any of the following:
- Presence of laboratory evidence of autoimmune disease (e.g., positive ANA titer) without symptoms
- Clinical evidence of vitiligo or other forms of depigmenting illness
- Mild arthritis requiring nonsteroidal anti-inflammatory medication
No autoimmune disorder with visceral involvement

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No recent (within the past year) or concurrent addiction to alcohol or illicit drugs
No other malignancy within the past 5 years except nonmetastatic squamous cell or basal cell skin cancer, ductal or lobular carcinoma in situ of the breast, or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 4 weeks since prior sargramostim (GM-CSF), interferon alfa-2b, or interleukin-2
No prior vaccination with any of the study peptides

Chemotherapy

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

Endocrine therapy

See Disease Characteristics
More than 30 days since prior systemic corticosteroids, including any of the following:
- Therapeutic doses of oral steroids (e.g., prednisone or dexamethasone)
- Steroid inhalers (e.g., Advair)
  - Topical steroids and nasal steroids with low systemic absorption (e.g., fluticasone) or steroids with low systemic absorption (e.g., triamcinolone hexacetonide) injected into a joint space allowed
No concurrent corticosteroids
No concurrent topical or systemic steroids

Radiotherapy

See Disease Characteristics
No prior radiotherapy to measurable disease
At least 4 weeks since prior local control or palliative radiotherapy and recovered
No concurrent radiotherapy

Surgery

See Disease Characteristics
Recovered from prior major surgery
No concurrent surgery

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00071981

Show 65 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Craig L. Slingluff, MD	University of Virginia
Investigator:	John M. Kirkwood, MD	UPMC Cancer Centers

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000335055, ECOG-E1602
Study First Received:	November 4, 2003
Last Updated:	July 29, 2009
ClinicalTrials.gov Identifier:	NCT00071981 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage IV melanoma
recurrent melanoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunologic Factors
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Adjuvants, Immunologic
Pharmacologic Actions
Melanoma

Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Freund's Adjuvant

ClinicalTrials.gov processed this record on November 25, 2009