Completed

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

0 criteria met from your profileSee at a glance how your profile meets each eligibility criteria.
What is being tested

incomplete Freund's adjuvant

+ multi-epitope melanoma peptide vaccine
+ sargramostim
Biological
Who is being recruted

Melanoma
+8

+ Neoplasms
+ Neoplasms by Histologic Type
Over 18 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: May 2005
See protocol details

Summary

Principal SponsorEastern Cooperative Oncology Group
Last updated: January 13, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: May 9, 2005Actual date on which the first participant was enrolled.

OBJECTIVES: * Compare the cytotoxic T-cell response to each of 12 melanoma peptides restricted by Human Leukocyte Antigen (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 Major histocompatibility complex (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 (Granulocyte-macrophage colony-stimulating factor, 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. ACTUAL ACCRUAL: A total of 175 patients were accrued for this study during March 2005 and January 2009.

Official TitleA Randomized Phase II Trial of Multi-Epitope Vaccination With Melanoma Peptides For Cytotoxic T Cells And Helper T Cells For Patients With Metastatic Melanoma 
NCT00464152NCT00071981
Principal SponsorEastern Cooperative Oncology Group
Last updated: January 13, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
175 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

None (Single-arm trial)
: If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment
: Everyone gets the same treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Skin Diseases
Skin Neoplasms
Neuroectodermal Tumors
Nevi and Melanomas
Neuroendocrine Tumors
Criteria

Inclusion Criteria: * Histologically confirmed stage IV melanoma * Multiple primary melanomas allowed * Metastasis may be from a cutaneous, mucosal, ocular, or unknown primary site * Measurable disease by Response Evaluation Criteria In Solid Tumors (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 * Human Lymphocyte Antigen (HLA)-A1, -A2, or -A3 positive * Prior brain metastases allowed provided all of the following are true: * 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 * Age: 18 and over * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Adequate organ function measured within 4 weeks before randomization: * White blood cell (WBC) at least 4,000/mm\^3 * Platelet count at least 100,000/mm\^3 * Lymphocyte count at least 700/mm\^3 * Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (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 * Creatinine no greater than 1.8 mg/dL * Negative pregnancy test * Fertile patients must use effective contraception * 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 * At least 4 weeks since prior sargramostim (GM-CSF), interferon alfa-2b, or interleukin-2 * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) * 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 * At least 4 weeks since prior local control or palliative radiotherapy and recovered * Recovered from prior major surgery Exclusion criteria: * More than 3 brain metastases * Metastatic lesions greater than 2 cm * Concurrent radiotherapy * Prior radiotherapy to measurable disease * Concurrent surgery * Concurrent corticosteroids * Concurrent topical or systemic steroids * Concurrent chemotherapy * Prior vaccination with any of the study peptides * Recent (within the past year) or concurrent addiction to alcohol or illicit drugs * Pregnant or nursing * Known or suspected major allergy to any components of the study vaccine * Significant detectable infection * Immunosuppression conditions * Prior or active autoimmune disorder requiring cytotoxic or mmunosuppressive therapy, except for any of the following: * Presence of laboratory evidence of autoimmune disease (e.g., positive antinuclear antibody (ANA) titer) without symptoms * Clinical evidence of vitiligo or other forms of depigmenting illness * Mild arthritis requiring nonsteroidal anti-inflammatory medication * Autoimmune disorder with visceral involvement


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
4 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group 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 (incomplete Freund's adjuvant) 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.

Given by injection

Given by injection

Given by injection
Group II
Experimental
Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 1 tetanus peptide melanoma vaccine emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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.

Given by injection

Given by injection

Given by injection

Given by injection
Group III
Experimental
Patients receive 2 injections of multi-epitope peptide vaccine comprising multi-epitope melanoma peptide vaccine (12MP) and 6 melanoma helper peptides (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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.

Given by injection

Given by injection

Given by injection

Given by injection
Group IV
Experimental
Patients receive 2 injections of multi-epitope peptide vaccine comprising melanoma helper peptide vaccine (6HP) emulsified with GM-CSF and ISA-51 (incomplete Freund's adjuvant) 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.

Given by injection

Given by injection

Given by injection
Study Objectives
Primary Objectives

Assessment of CTL response was based on a fold-increase in T cell response measure by interferon-gamma ELIspot assay.
Secondary Objectives

Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.

Helper T cell response was evaluated by tritiated thymidine proliferation assay with fresh/cryopreserved PBL in the presence of each of the helper peptides.

Tumor response was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Objective response rate is calculated as the number of patients with complete response (disappearance of all lesions) or partial response () divided by total number of evaluable patients.

OS was defined as the time from registration to death from any cause.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 65 locations
Suspended
Veterans Affairs Medical Center - Palo AltoPalo Alto, United StatesSee the location
Suspended
Stanford Cancer CenterStanford, United States
Suspended
Tunnell Cancer Center at Beebe Medical CenterLewes, United States
Suspended
CCOP - Christiana Care Health ServicesNewark, United States

Completed65 Study Centers
;