EF5 in Treating Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003282
First received: November 1, 1999
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

Diagnostic procedures using the drug EF5 to detect the presence of oxygen in tumor cells may help to plan effective treatment for solid tumors. 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: therapeutic conventional surgery
Procedure: biopsy
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Phase I Trial of EF5, an Agent for the Detection of Hypoxia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Pharmacokinetics parameters including estimation of Cmax, half-life, and area under the time-concentration curve (AUC) [ Time Frame: Pre-dose, 1, 24, and 28 hours ] [ Designated as safety issue: No ]
  • Acute toxicity graded by NCI/DCTDC Common Toxicity Criteria [ Time Frame: Up to 24 hours ] [ Designated as safety issue: Yes ]
  • Late toxicity graded by NCI/DCTDC Common Toxicity Criteria [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity defined as any grade III or higher toxicity [ Time Frame: Up to 45 days ] [ Designated as safety issue: Yes ]
  • Acceptable signal-to-noise ratio (75 or above) [ Time Frame: Up to 45 days ] [ Designated as safety issue: No ]
  • Safe and effective dose defined as the dose at which less than 2 of 6 patients have dose-limiting acute or late toxicity and the mean value of signal-to-noise ratio is greater than or equal to 75 [ Time Frame: Up to 45 days ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: March 1998
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diagnostic (EF5)
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.
Drug: EF5
Given IV
Procedure: therapeutic conventional surgery
Undergo resection
Procedure: biopsy
Undergo biopsy
Other Name: biopsies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the optimal dose of etanidazole derivative EF5 that is safely tolerated and provides optimal signal-to-noise ratio in patients with solid tumors.

II. Determine the toxic effects of EF5 in this patient population. III. Determine the pharmacokinetics of EF5 in this patient population. IV. Determine the dose of EF5 that provides a mean signal-to-noise ratio (maximum binding in anoxia to minimum binding) of 75.

V. Determine the relationship between tumor oxygenation by EF5 binding and needle electrode measurements.

VI. 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

Inclusion Criteria:

  • 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
  • Performance status - ECOG 0-2
  • Life expectancy not specified
  • WBC greater than 2,000/mm^3
  • Platelet count greater than 100,000/mm^3
  • Bilirubin less than 2.0 mg/dL
  • Creatinine less than 2.0 mg/dL
  • Creatinine clearance greater than 50 mL/min
  • No significant cardiac disease that would preclude the safe use of general anesthesia
  • No significant pulmonary disease that would preclude the safe use of general anesthesia
  • 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
  • See Disease Characteristics
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen Michael Hahn Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003282     History of Changes
Other Study ID Numbers: NCI-2012-02266, UPCC 7597, R01CA075285, CDR0000066191
Study First Received: November 1, 1999
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

ClinicalTrials.gov processed this record on October 23, 2014