Protocol Number: 06-C-0069

Title:

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

Number:

06-C-0069

Summary:

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 HLA-A2, through a specific blood test, may be eligible for this study.

Up to 145 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 assigned to groups 5-6 by chance, like a flip of a coin ; a process called randomization. Patients are being randomized to groups 5 and 6 which were recently added since preliminary results from the other groups indicate that the peptide was not immunizing. We believe this is due to non-optimal preparation of the peptide and adjuvant. Therefore, groups 5 and 6 were added with a new way of preparation of the peptide and adjuvant which others have shown to immunize. 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. Group 5 will receive the peptide with an adjuvant oil-based liquid called "Montanide ISA-51 VG"(Montanide). This adjuvant (or "assistant") is intended to increase the reaction of your immune system to the peptide. This will be given as an injection in your thigh. The peptide and adjuvant will be mixed using 2 syringes. Group 6 will receive gp100, Montanide (as an injection in your thigh) and a cream called imiquimod applied to the skin for 5 days. Imiquimod has been approved by the U.S. Food and Drug Administration (FDA) for treatment of superficial basal carcinoma, actinic keratosis, genital warts and herpes and we think that this drug may help the immune cells in your skin recognize the vaccine, but we do not know this for certain. The peptide and adjuvant will be mixed using 2 syringes. 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.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

HLA-A 0201 patients, age greater than or equal to16 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 AST/ALT less than three times normal,

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 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 WBC count 8 an/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.

Special Instructions:

Currently Not Provided

Keywords:

Disease Free Survival

gp 100:209-217 (210m)

Immunologic Response

Adjuvant Therapy

Cutaneous Melanoma

Recruitment Keyword(s):

Melanoma

Cutaneous Melanoma

Condition(s):

High-Risk Melanoma

Investigational Drug(s):

gp100:209-217 (210M)

Montanide ISA-51

Investigational Device(s):

None

Intervention(s):

Drug: gp100:209-217 (210M)

Drug: Montanide ISA-51

Supporting Site:

National Cancer Institute

Contact(s):

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
Phone: (866) 820-4505
Fax: (301) 451-1927
Electronic Address: ncisbirc@mail.nih.gov

Citation(s):

Rosenberg SA, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994 Mar 23-30;271(12):907-13.

Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52.

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9.

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