Evaluation of the Impact of Adjuvants Accompanying Peptide Immunization in High-Risk Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Steven Rosenberg, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00273910
First received: January 7, 2006
Last updated: October 17, 2012
Last verified: October 2012
  Purpose

This study will evaluate the immunization effects of a vaccine for patients who are at risk for recurrence of their skin cancer. That is, the risk of cancer is higher if melanoma has invaded deep into the skin or lymph nodes. Currently, the only therapy that the U.S. Food and Drug Administration (FDA) has approved for preventing recurrence of melanoma is alpha-interferon. But the research data are controversial. In this study, the vaccine to be used, called gp100, contains a piece of a protein called a peptide, which melanoma cancer cells produce.

Patients 16 and older who have had confirmed melanoma surgically removed and whose tissue type is tested as being human leukocyte antigen serotype within HLA-A serotype group (HLA-A2), through a specific blood test, may be eligible for this study.

Up to 132 participants will be enrolled. There will be a physical examination and collection of blood samples for tests, and making sure that x-rays and scans are current. Patients will be randomly assigned to four groups. Group 1 will receive the peptide with an adjuvant (assistant) oil-based liquid called Montanide ISA-51, as an injection in the thigh. Group 2 will receive gp100, Montanide, and a cream called imiquimod, which the FDA has approved for treating genital warts and herpes but that may help immune cells in the skin to recognize the vaccine. Imiquimod will be applied to the skin for 5 days. Group 3 will receive gp100 mixed in salt water given as several mini-doses under the skin of the thigh. Group 4 will also receive several mini-doses of gp100 mixed in saline, as well as imiquimod cream applied to the skin for 5 days. All patients will receive the gp100 every 3 weeks for 12 weeks. Every dose is a cycle, with four cycles considered a course of therapy. If the melanoma does not return or patients do not experience side effects from this therapy, then the courses of vaccine will repeated for up to 12 cycles of therapy (3 courses over 33 weeks). Side effects of the peptide vaccination include local swelling, swelling of local lymph nodes, bruising, and pain and redness at the injection sites. There may be chills or fever. Patients will be watched closely for such side effects.

To study how the vaccine changes the action of cells in the immune system, patients' white blood cells (lymphocytes) will be obtained, involving a separate informed consent. The procedure, called leukaphersis, requires inserting a needle into the arm, to obtain blood going into a machine, which divides the blood into red cells, plasma (or the serum part), and lymphocytes. The lymphocytes are removed, and the plasma and red cells returned to the patient through a second needle in the other arm. Risks associated with the procedure include fainting, which can be prevented by patients' eating before coming to the lab, and bleeding and infection at the needle site. Patients will undergo leukapheresis will be done about four times: before receiving the vaccine, 3 weeks after the first four doses, and then after 8 cycles and 12 cycles. Patients assigned to the groups receiving imiquimod will be asked to record every time they apply that cream and describe any symptoms developed during the study. All patients will be watched closely for any sign that their melanoma has returned. Before and throughout the study, multiple blood tests will be conducted.

The vaccine, Montanide, and imiquimod may increase patients' immune system in fighting off new tumors, but that is not known now. However, the study may provide information that will be useful in treating melanoma patients in the future.


Condition Intervention Phase
High-Risk Melanoma
Drug: gp100:209-217 (210M)
Drug: Montanide ISA-51
Drug: Imiquimod
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Impact of Adjuvants Accompanying Peptide Immunization in High Risk Melanoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Immunologic Response Rate [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Comparison of six different preparations of the gp100:209-217 (210M) melanoma antigen peptide. The arm with the greater number of immunologic responses will be the one most likely to be selected for future study on the basis of immunization alone. Evidence of immunization consist of at least 10 Elispots/100,000 cells above background. An injection site reaction is not an immune response.


Secondary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
    Here are the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.


Enrollment: 104
Study Start Date: January 2006
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adj-3 A2 gp209(2M) in IFA SQ (vortex)
gp100:209-217(210M) peptide emulsified in MONTANIDE ISA-51 or Montanide ISA 51 VG injected subcutaneously on day one every three weeks (1 cycle) for a total of twelve cycles (33 weeks).
Drug: gp100:209-217 (210M) Drug: Montanide ISA-51
Experimental: Adj-3 A2 gp209(2M) in IFA SQ + Imiquimod (vortex)
gp100:209-217(210M) peptide emulsified in MONTANIDE ISA-51 or Montanide ISA 51 VG injected subcutaneously on day one every three weeks (1 cycle) for a total of twelve cycles (33 weeks); following the injection patients will apply imiquimod to the skin at the site of injection daily for 5 days.
Drug: gp100:209-217 (210M) Drug: Montanide ISA-51 Drug: Imiquimod
Apply imiquimod 5% cream to the skin at the site of injection daily for 5 days
Other Name: Aldara
Experimental: Adj-3 A2 gp209(2M) in saline ID
gp100:209-217(210M) in 0.9% Sodium Chloride Injection injected intradermally on day one every three weeks (1 cycle) for a total of twelve cycles (33 weeks).
Drug: gp100:209-217 (210M)
Experimental: Adj-3 A2 gp209(2M) in saline ID + Imiquimod
gp100:209-217(210M) peptide in 0.9% Sodium Chloride Injection injected intradermally on day one every three weeks (1 cycle) for a total of twelve cycles (33 weeks); following the injection patients will apply imiquimod to the skin at the site of the injection daily for 5 days.
Drug: gp100:209-217 (210M) Drug: Imiquimod
Apply imiquimod 5% cream to the skin at the site of injection daily for 5 days
Other Name: Aldara
Experimental: Adj-3 A2 gp209(2M) in IFA SQ (2 Syringe)
gp100:209-217(210M) peptide emulsified in Montanide ISA 51 VG injected subcutaneously on day one every three weeks (1 cycle) for a total of twelve cycles (33 weeks).
Drug: gp100:209-217 (210M) Drug: Montanide ISA-51
Experimental: Adj-3 A2 gp209(2M) in IFA SQ + Imiquimod (2 Syringe)
gp100:209-217(210M) peptide emulsified in Montanide ISA 51 VG injected subcutaneously on day one every three weeks (1 cycle) for a total of twelve cycles (33 weeks); following the injection patients will apply imiquimod to the skin at the site of injection daily for 5 days.
Drug: gp100:209-217 (210M) Drug: Montanide ISA-51 Drug: Imiquimod
Apply imiquimod 5% cream to the skin at the site of injection daily for 5 days
Other Name: Aldara

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

HLA-A 0201 patients, age greater than or equal to 16 years, primary melanomas with lesions that are ulcerated and greater than or equal to 2mm, or any lesions that are greater than or equal to 4.0 mm in thickness, or greater than or equal to1 positive lymph node, or local recurrence, or resected metastatic disease, within 6 months of surgical resection will be considered. Patients must be clinically disease free at the time of protocol entry as documented by radiologic studies within 6 weeks of patient entry.

Serum creatinine of 2.0 mg/dl or less

Total bilirubin 1.6 mg/dl or less, except for patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

WBC 3000/mm^3 or greater,

Platelet count 90,000 mm^3 or greater,

Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than three times normal,

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients of both genders must be willing to practice effective birth control during this trial because the potential for teratogenic effects are unknown.

Patients may have had prior adjuvant treatment with immunotherapy, including interferon, as long as 3 weeks have elapsed since prior systemic therapy.

EXCLUSION CRITERIA:

Patients will be excluded:

Who have ocular or mucosal melanoma.

Who are undergoing or have undergone in the past 3 weeks any systemic therapy except surgery for their cancer, and must have recovered to a grade I from any adverse effects of treatment prior to entry, other than those that do not have clinical implications, e.g. vitiligo, alopecia.

Have active systemic infections, autoimmune disease or any known immunodeficiency disease.

Who require systemic steroid therapy.

Who are pregnant (because of possible side effects on the fetus) or breastfeeding because of unknown effects on the developing child).

Who are known to be positive for hepatitis BsAG or human immunodeficiency virus (HIV) antibody (because of possible immune effects of these conditions).

Who have any form of autoimmune disease (such as autoimmune colitis or Crohn's Disease) or immunodeficiency as evidenced by abnormal white blood count (WBC) count 8 and/or presence of opportunistic infections. Must have recovered immune competence after radiation therapy. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)

Who have previously been immunized with gp100.

Who have known hypersensitivity to any of the agents used in this study.

Who have previously received chemotherapy for treatment of melanoma.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00273910

Locations
United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute, National Institutes of Health
  More Information

Additional Information:
Publications:
Responsible Party: Steven Rosenberg, Dr. Steven Rosenberg, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00273910     History of Changes
Obsolete Identifiers: NCT00304057
Other Study ID Numbers: 060069, 06-C-0069
Study First Received: January 7, 2006
Results First Received: March 30, 2012
Last Updated: October 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Disease Free Survival
gp 100:209-217 (210m)
Immunologic Response
Adjuvant Therapy
Cutaneous Melanoma
Melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Imiquimod
Freund's Adjuvant
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers

ClinicalTrials.gov processed this record on September 11, 2014