Protocol Number: 01-C-0032

Title:

Immunization of HLA-A*0201 or HLA-DPB1*04 Patients with Metastatic Cancer Using Epitopes from the ESO-1 Antigen

Number:

01-C-0032

Summary:

This study will test the safety and effectiveness of an experimental vaccine for fighting metastatic cancer-that is, disease that has spread from the primary site. The vaccine contains a peptide (piece of a protein) called ESO-1, which is made by several different kinds of cancers. It also contains an oil-based liquid called Montanide ISA-51, another experimental substance that is intended to boost the immune reaction to the peptides.

Patients 16 years of age and older with metastatic cancer that does not respond to standard treatment may be eligible for this study. Candidates will be screened with a physical examination, chest X-ray, electrocardiogram blood and urine tests, and X-rays and scans to the evaluate the extent and size of the tumor. Because the vaccine formulation is based on tissue type, participants will have a biopsy or blood test to determine that their tissue type is HLA-A*0201 and that their tumor produces the ESO-1 peptide. Depending on the type and location of tumor, the biopsy may be done with a needle (needle biopsy), with a small sharp cookie-cutter instrument (punch biopsy), or with a small knife (excisional biopsy).

Participants will be randomly assigned to receive vaccine either once a week for 10 weeks; once every 3 weeks for four times, or four times a week every 3 weeks for four times. The vaccine is given as an injection (shot) in the thigh. Treatment will continue for 12 weeks, and a physical examination and blood tests will be done at each treatment visit to monitor side effects.

About 40 cc (8 teaspoons) of blood will be drawn every 3 weeks to monitor body functions. Patients will undergo leukapheresis to evaluate how the vaccine affects the action of lymphocytes-important white blood cells of the immune system. In this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The lymphocytes are then removed and the rest of the blood-red cells, platelets and plasma-is returned to the body through a second needle in the other arm. Patients who receive weekly injections will have the procedure before their first vaccination and after the last vaccination; those who receive injections every 3 weeks will also have the procedure between their second and third vaccinations.

Patients will return for follow-up studies 3 weeks after the fourth weekly injection, or after the second and fourth injection for those on the every-3-weeks injection schedule. If the tumor has responded to the vaccine, the treatment may be repeated on the same schedule for up to 12 months, with continuing follow-up visits. Some patients may have a needle biopsy of normal skin and tumor or lymph node to examine the effects of the vaccine on the immune cells in the tumor.

Patients whose cancer returns during or after peptide treatment may be given a drug called interleukin-2 (IL-2), to boost the immune reaction to the tumor. IL-2 is infused through a vein over 15 minutes, and is given every 8 hours for 4 days after each vaccine injection.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Any patient age greater than or equal to 16 years with measurable or evaluable metastatic melanoma who is HLA-A*0201 or HLA-DPB*04, has progressed while receiving standard treatment and has an expected survival of greater than three months will be considered.

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 of 3.0 mg/dl or less.

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 or 2.

Patients of both genders must be willing to practice effective birth control during this trial.

Demonstration of ESO-1 expression by analysis of RT-PCR amplified tissue, or the presence of serum antibody of ESO-1.

EXCLUSION CRITERIA:

Patients will be excluded:

Who are undergoing or have undergone in the past 3 weeks any systemic therapy for their cancer.

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).

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 active primary or secondary immunodeficiency or who have not recovered immune competence after chemotherapy or radiation therapy as evidenced by abnormal lymphocyte counts or presence of opportunistic infections.

Who have previously been immunized to ESO-1.

To be eligible to receive IL-2, patients may not have active major medical illnesses such as cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

To be eligible to receive IL-2, patients must be willing to sign a durable power of attorney (DPA).

Patients with lung cancer will not be included.

Special Instructions: Currently Not Provided

Keywords:

Vaccine

Immunologic Response

Clinical Response

Toxicity

Randomization

Recruitment Keywords:

None

Conditions:

Cancer

Investigational Drug(s):

IL-2

ESO-1:157-165 (165V)

Montanide ISA-51

(161-180) ESO-1

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Cloning of the gene coding for a shared human melanoma antigen recognized by autologous t cells infiltrating into tumor

Simultaneous humoral and cellular immune response against cancer testis antigen ny-eso-1: definition of human histocompability lekocyte antigen (hla) - a2-binding peptide epitopes

Enhancement of cellular immunity in melanoma patients immunized with a peptide from mart-1/melan a

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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Bethesda, Maryland 20892. Last update: 10/16/2004