Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Anakinra in Treating Patients With Metastatic Cancer Expressing the Interleukin-1 Gene

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	NCI-03-C-0281 NCT00072111

Objectives

Primary

1. Determine the maximum tolerated dose and dose-limiting toxicity of anakinra in patients with metastatic cancer expressing the interleukin-1 gene.
2. Determine the steady state pharmacokinetics of this drug in these patients.

Secondary

1. Determine the antitumor efficacy of this drug in these patients.
2. Determine gene expression changes in tumor biopsies and circulating leukocyte and cytokine levels in these patients before and after treatment with this drug.

Entry Criteria

Disease Characteristics:

• Diagnosis of metastatic cancer



• Measurable disease
  • Able to be percutaneously biopsied with minimum morbidity on protocol NCI-99-C-0128



• Tumor expression of interleukin-1 by biopsy



• Progressive disease during prior standard first-line chemotherapy OR refused standard first-line chemotherapy



• No active intracranial or leptomeningeal metastases
  • Prior radiotherapy to or resection of intracranial metastatic disease allowed provided there is no evidence of active disease on MRI or CT scan for the past month AND there is no requirement for concurrent anticonvulsant or steroid medications

Prior/Concurrent Therapy:

Biologic therapy

• More than 30 days since prior biologic therapy
• No concurrent systemic immune modulators

Chemotherapy

• See Disease Characteristics
• More than 30 days since prior chemotherapy

Endocrine therapy

• See Disease Characteristics
• No concurrent steroids

Radiotherapy

• See Disease Characteristics
• More than 14 days since prior localized radiotherapy to non-target lesions and recovered
• More than 30 days since other prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 30 days since prior antibiotic therapy for infection

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 4 months

Hematopoietic

• Platelet count greater than 75,000/mm³
• Absolute neutrophil count greater than 1,500/mm³

Hepatic

• PT within 2 seconds of the upper limit of normal
• Bilirubin less than 1.5 mg/dL

Renal

• Creatinine no greater than 1.6 mg/dL

  OR

• Creatinine clearance greater than 30 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• No allergy to proteins made from bacteria
• No active infection
• HIV negative

Expected Enrollment

A total of 3-24 patients will be accrued for this study within 1-2 years.

Outline

This is a dose-escalation study.

Patients receive anakinra subcutaneously 1-3 times daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of anakinra until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients are treated at that dose.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Steven Libutti, MD, Principal investigator		Ph: 301-496-5049 Email: steven_Libutti@nih.gov

Related Information

PDQ® clinical trial NCI-99-C-0128

Registry Information
Official Title		Phase I Study of Anakinra Mediated Tumor Regression and Angiogenesis Inhibition in Subjects with Cancers Producing Interleukin-1
Trial Start Date		2003-09-17
Registered in ClinicalTrials.gov		NCT00072111
Date Submitted to PDQ		2003-09-17
Information Last Verified		2006-04-01