Protocol Number: 03-C-0281

Title:

Phase I Study of Anakinra Mediated Tumor Regression and Angiogenesis Inhibition in Patients with Cancers Producing Interleukin-1

Number:

03-C-0281

Summary:

This study will determine the maximum safe dose and side effects of the drug anakinra in patients with advanced cancer whose tumors produce a protein called interleukin-1. Approved by the Food and Drug Administration to treat rheumatoid arthritis, anakinra has shown potential for shrinking or slowing the progression of certain tumors that make interleukin-1.

Patients 18 years of age and older with cancer that has spread from the primary site and whose tumor can be biopsied may be eligible for this study. Patients must have disease that has progressed after receiving standard chemotherapy or must have refused standard chemotherapy. Candidates will be screened with a medical history and physical examination, blood and urine tests, electrocardiogram, and imaging studies (x-rays, CT and MRI scans) to evaluate the location and extent of tumor. They will also have a tumor biopsy to determine if their tumor produces interleukin-1, a requirement for the study. For the biopsy, a small area of skin is numbed and a small piece of tumor is removed, either with a needle or by a small cut in the tumor.

Participants will receive treatment with anakinra, given as a shot under the skin. Patients or a caregiver will be taught how to administer the injections. The dose of anakinra will be increased over time with different patients in a process called dose escalation in order to determine the most effective, yet safe, dose of the drug. Patients will be have blood tests weekly to determine blood levels of the drug, and a tumor biopsy and physical evaluation will be done every 2 months to evaluate response to therapy and side effects. Patients whose tumor remains stable or shrinks may be offered continued therapy for up to 6 months. Beyond that, continuation of therapy will be discussed between patient and physician. Patients whose tumor continues to grow while receiving anakinra will be taken off the study and alternative therapies will be discussed.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Patients with measurable metastatic cancer are eligible for evaluation. Patients must have disease that can be biopsied percutaneously with minimum morbidity on protocol 99-C-0128.

Patients must have progressed while receiving standard first line chemotherapy or be unwilling to receive standard first line chemotherapy for their cancer.

Patients must have had no chemotherapy, biologic therapy, or radiation therapy for their malignancy within 30 days prior to study entry. Patients may have received localized radiation therapy to non-target lesions provided that the radiotherapy is completed 14 days prior to commencing therapy, and the patient has recovered from any toxicity.

Patients must have an ECOG performance status of less than or equal to 2.

Patients must not have had any serious infection requiring antibiotic therapy for at least 30 days prior to inclusion on the study.

Patients must be 18 years of age or older due to unknown effects of this drug in this drug in this pediatric population.

Patients must have a platelet count greater than 75,000, an absolute neutrophil count greater than 1500/micro L, a PT within 2 seconds within the upper limit of normal, a total bilirubin of less than 1.5 mg/dL, and a serum creatinine less than or equal to 1.6 mg/ml unless the creatinine clearance greater than 30 mL/min/1.73 m(2).

Patients must be willing to sign an informed consent, and undergo tumor biopsies to evaluate for alteration in IL-1 gene expression.

Patients must have a tumor biopsy that constitutively expresses IL-1.

EXCLUSION CRITERIA:

Patients with non-measurable metastatic cancer or metastatic tumors which cannot be readily biopsied.

Patients with active intracranial and leptomeningeal metastases will be excluded. Patients who have received resection or radiation therapy for intracranial metastatic disease may be eligible provided there is no evidence of active disease on MRI scan for greater than one month prior to commencing treatment and they require no anticonvulsant medication or steroids to control residual symptoms.

Patients with life expectancy less than 4 months will be excluded.

Patients who require systemic immune modulating medications including steroids will be excluded.

Pregnant patients and lactating mothers will be excluded due to the unknown, potentially harmful effects of this agent on fetal and early childhood development.

Patients with active infections will be excluded.

Patients HIV will be excluded due to the potential risk of opportunistic infection.

Special Instructions: Currently Not Provided

Keywords:

Open-Histology

Cytokine

Maximum Tolerated Dose

Dose Limited Toxicity

Gene Expression Changes

Recruitment Keywords:

Cancer

Metastatic Cancer

Conditions:

Neoplasms

Investigational Drug(s):

None

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:

Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ.

Cancer statistics, 2003. CA Cancer J Clin. 2003 Jan-Feb;53(1):5-26.

Vidal-Vanaclocha F, Amezaga C, Asumendi A, Kaplanski G, Dinarello CA. Interleukin-1 receptor blockade reduces the number and size of murine B16 melanoma hepatic metastases.

Cancer Res. 1994 May 15;54(10):2667-72.

Chirivi RG, Garofalo A, Padura IM, Mantovani A, Giavazzi R.

Interleukin 1 receptor antagonist inhibits the augmentation of metastasis induced by interleukin 1 or lipopolysaccharide in a human melanoma/nude mouse system. Cancer Res. 1993 Oct 15;53(20):5051-4.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

Warren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/16/2004