EF5 in Treating Patients With Solid Tumors - Full Text View

Sponsors and Collaborators:	University of Pennsylvania National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003282

Purpose

RATIONALE: Diagnostic procedures using the drug EF5 to detect the presence of oxygen in tumor cells may help to plan effective treatment for solid tumors.

PURPOSE: This phase I trial is studying how well EF5 works in detecting the presence of oxygen in tumor cells in patients with solid tumors that can be biopsied or removed by surgery.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: EF5 Procedure: conventional surgery Procedure: fluorescent antibody technique	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Immunoglobulins Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase I Trial of EF5, an Agent for the Detection of Hypoxia

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

February 1998

Detailed Description:

OBJECTIVES:

Determine the optimal dose of etanidazole derivative EF5 that is safely tolerated and provides optimal signal-to-noise ratio in patients with solid tumors.
Determine the toxic effects of EF5 in this patient population.
Determine the pharmacokinetics of EF5 in this patient population.
Determine the dose of EF5 that provides a mean signal-to-noise ratio (maximum binding in anoxia to minimum binding) of 75.
Determine the relationship between tumor oxygenation by EF5 binding and needle electrode measurements.
Compare the levels of EF5 binding in regions of low and high blood flow.

OUTLINE: This is a dose-escalation study.

Patients receive etanidazole derivative EF5 IV over 1-2 hours beginning approximately 24 hours prior to surgery. Tumors are then resected or biopsied after Eppendorf needle electrode measurements.

Cohorts of 6 patients receive escalating doses of EF5 until the maximum tolerated dose (MTD) or optimal dose is determined. The MTD is defined as the dose preceding that at which 2 or more patients experience dose-limiting toxicity. The optimal dose is defined as the dose level at or below the MTD and results in a signal-to-noise ratio of 75 or greater. Thirty additional patients are treated at the optimal dose.

Patients are followed at 30-45 days post EF5 infusion.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed tumor or highly suspicious cancerous mass based on imaging and clinical signs but not indicative of a direct biopsy/cellular diagnosis preceding surgery
Must have a clinical condition or physiologic status which demonstrates that the appropriate or standard initial therapy for the tumor is surgical biopsy or resection

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

WBC greater than 2,000/mm^3
Platelet count greater than 100,000/mm^3

Hepatic:

Bilirubin less than 2.0 mg/dL

Renal:

Creatinine less than 2.0 mg/dL OR
Creatinine clearance greater than 50 mL/min

Cardiovascular:

No significant cardiac disease that would preclude the safe use of general anesthesia

Pulmonary:

No significant pulmonary disease that would preclude the safe use of general anesthesia

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 1 month after study
No history of grade III or IV peripheral neuropathy

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003282

Locations

United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283

Sponsors and Collaborators

University of Pennsylvania

National Cancer Institute (NCI)

Investigators

Study Chair:

Stephen Michael Hahn, MD

University of Pennsylvania

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

Evans SM, Hahn SM, Magarelli DP, Koch CJ. Hypoxic heterogeneity in human tumors: EF5 binding, vasculature, necrosis, and proliferation. Am J Clin Oncol. 2001 Oct;24(5):467-72.

Evans SM, Hahn SM, Magarelli DP, Zhang PJ, Jenkins WT, Fraker DL, Hsi RA, McKenna WG, Koch CJ. Hypoxia in human intraperitoneal and extremity sarcomas. Int J Radiat Oncol Biol Phys. 2001 Feb 1;49(2):587-96.

Koch CJ, Hahn SM, Rockwell K Jr, Covey JM, McKenna WG, Evans SM. Pharmacokinetics of EF5 [2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] in human patients: implications for hypoxia measurements in vivo by 2-nitroimidazoles. Cancer Chemother Pharmacol. 2001 Sep;48(3):177-87.

Evans SM, Hahn S, Pook DR, Jenkins WT, Chalian AA, Zhang P, Stevens C, Weber R, Weinstein G, Benjamin I, Mirza N, Morgan M, Rubin S, McKenna WG, Lord EM, Koch CJ. Detection of hypoxia in human squamous cell carcinoma by EF5 binding. Cancer Res. 2000 Apr 1;60(7):2018-24.

Ziemer LS, Koch CJ, Maity A, Magarelli DP, Horan AM, Evans SM. Hypoxia and VEGF mRNA expression in human tumors. Neoplasia. 2001 Nov-Dec;3(6):500-8.

Evans SM, Judy KD, Dunphy I, Jenkins WT, Hwang WT, Nelson PT, Lustig RA, Jenkins K, Magarelli DP, Hahn SM, Collins RA, Grady MS, Koch CJ. Hypoxia is important in the biology and aggression of human glial brain tumors. Clin Cancer Res. 2004 Dec 15;10(24):8177-84.

Evans SM, Judy KD, Dunphy I, Jenkins WT, Nelson PT, Collins R, Wileyto EP, Jenkins K, Hahn SM, Stevens CW, Judkins AR, Phillips P, Geoerger B, Koch CJ. Comparative measurements of hypoxia in human brain tumors using needle electrodes and EF5 binding. Cancer Res. 2004 Mar 1;64(5):1886-92.

Study ID Numbers:	CDR0000066191, UPCC-7597, NCI-T97-0045, UPCC-1663-0
Study First Received:	November 1, 1999
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00003282
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Antibodies
Immunoglobulins

ClinicalTrials.gov processed this record on January 14, 2009