Protocol Number: 03-C-0094

Title:

A Phase II Open Label Study Of Single Agent MDX-010 For The Treatment of IL-2 Refractory or IL-2 Ineligible Patients With Stage IV Renal Cancer

Number:

03-C-0094

Summary:

This study will evaluate the safety and effectiveness of the experimental drug MDX-010 in treating patients with stage IV kidney cancer. MDX-010 is an antibody to the CTLA-4protein found on certain lymphocytes (a type of white blood cell) that helps stop an immune response. When lymphocytes recognize a foreign substance, such as a virus or bacteria, they initiate an immune response to fight and control the infection. Once this is achieved, CTLA-4 protein help stop the immune response, decreasing the number of immune cells against the specific virus or bacteria. When an immune response is mounted against tumor cells, however, it may be beneficial not to stop the immune response, but instead, to keep a large number of lymphocytes available to recognize and fight tumor cells. In this study, MDX-010 will be used to block CTLA-4 and maintain immune activity.

Patients 16 years of age and older who have kidney cancer that has spread to the lymph nodes or other sites and who have either not benefited from standard treatment with interleukin-2 or cannot receive interleukin-2 for medical reasons may be eligible for this study. Candidates will be screened with a history, physical examination, eye examination, blood and urine tests, electrocardiogram (EKG), lung function tests, and computed tomography (CT) or magnetic resonance imaging (MRI) scans to evaluate the size and extent of their tumor.

Participants will receive up to four MDX-010 treatments 28 days apart. Each treatment consists of a dose of MDX-010 given intravenously (through a vein) via a catheter (thin plastic tube) over 90 minutes. In addition to the drug treatment, patients will have the following tests and procedures:

- Blood tests every 28 days (every treatment visit) to look for side effects and the body's reaction to he treatment.

- Leukapheresis to study the effects of treatment on the immune system. For this procedure, blood is drawn through a needle in an arm vein and circulated through a machine that separates the blood into its components (red cells, white cells, platelets, and plasma). The lymphocytes are extracted and the rest of the blood is returned to the patient through a needle in the other arm.

- Biopsy of normal skin and tumor or lymph node to examine the effects of antibody on the immune cells in the tumor. For this procedure, a needle is put into the skin or tumor and a small amount of tissue is pulled out with the needle. Biopsies are optional; they are not required for participation in the study.

- Follow-up visits 4 weeks after the second and fourth treatments for checkup examination, scans and X-rays, and blood tests.

Patients will be watched closely for treatment side effects. Those who develop severe drug side effects, whose body develops an immune reaction against the MDX-010 antibody, or whose condition worsens during treatment may be taken off the study.

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 greater than or equal to 16 years of age with histologic diagnosis of stage IV clear cell renal carcinoma that is clinically evaluable, with at least one site of measurable disease.

Patients must have either had IL-2 therapy previously and shown tumor progression, or if they have not had IL-2 previously, must be ineligible to receive the standard FDA-approved high dose intravenous IL-2 regimen due to co-morbid medical conditions; or must have minimal disease (defined as lesions no greater than 3 cm that do not pose risk to organ function) or have indolent disease (defined as increase in tumor size of less than 50 percent over prior 6 months) where participation in this trial is not likely to compromise their opportunity to receive high dose IL-2 at a later time.

Patients must be greater than or equal to 3 weeks beyond their last treatment (radiation, hormone, immuno-, etc., therapy) for renal carcinoma and recovered from any serious toxicity experienced during treatment.

Women should be either: post-menopausal for at least one (1) year; surgically incapable of bearing children; or utilizing a reliable form of contraception. Women of childbearing potential must have a negative urine pregnancy test conducted during screening.

Because the risk of a negative influence of this therapy on reproductive processes, men who may father a child must agree to the use of male contraception for the duration of their participation in the trial.

Life expectancy greater than or equal to 3 months.

ECOG performance status les than 2.

Required values for initial laboratory test:

-WBC greater than or equal to 2500/ml

-ANC greater than or equal to 1500/ml

-Platelets greater than or equal to 100 x 10(3)/ml

-Hemoglobin greater than or equal to 10 g/dl

-Hematocrit greater than or equal to 30%

-Creatine less than 2.0 mg/dl

-AST less than or equal to 3 x ULN

-Bilirubin less than or equal to 1.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dl)

-HBsAg negative

-HIV negative

-Anti-HCV nonreactive

EXCLUSION CRITERIA:

Any other prior malignancy, except for the following: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer from which the patient has been disease-free for five (5) years or more.

A diagnosis of renal cancer of the true papillary, medullary, chromophobe, collecting duct or oncocytic types.

Autoimmune disease (including uveitis and autoimmune inflammatory eye disease) prior to the study.

Active uncontrolled infection, this includes positive results from HIV, HBsAg and anti-HCV.

Pregnancy or nursing: due to the possibility that MDX-010 could have a detrimental effect on the developing immune system of the fetus or infant, exposure in utero or via breast milk will not be allowed.

Any underlying medical condition which, in the opinion of the principal investigator, will make the administration of study drugs hazardous or obscure the interpretation of adverse events.

Any concurrent medical condition requiring the use of systemic or topical corticosteroids or the use of immunosuppressive agents (e.g. cyclosporin and its analog, or chemotherapy agents). All corticosteroid use must have been discontinued greater than four (4) weeks prior to trial entry.

Prior treatment with MDX-010.

Special Instructions: Currently Not Provided

Keywords:

Clear Cell Renal Cancer

Monoclonal Antibody (mAb)

Response Rate

Tumor Regression

Recruitment Keywords:

Renal Cancer

Kidney Cancer

Conditions:

Kidney Neoplasm

Investigational Drug(s):

MDX-010

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:

deKernion JB, Sarna G, Figlin R, Lindner A, Smith RB. The treatment of renal cell carcinoma with human leukocyte alpha-interferon. J Urol. 1983 Dec;130(6):1063-6. PMID: 6644883

Muss HB, Costanzi JJ, Leavitt R, Williams RD, Kempf RA, Pollard R, Ozer H, Zekan PJ, Grunberg SM, Mitchell MS, et al. Recombinant alfa interferon in renal cell carcinoma: a randomized trial of two routes of administration. J Clin Oncol. 1987 Feb;5(2):286-91 PMID: 3543247

Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet. 1999 Jan 2;353(9146):14-7. PMID: 10023944

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