Phase I Trial of EF5, an Agent for the Detection of Hypoxia
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Pharmacokinetics parameters including estimation of Cmax, half-life, and area under the time-concentration curve (AUC)
Study Overview
Brief Summary
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
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: EF5 (Drug)
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.
Intervention: therapeutic conventional surgery (Procedure)
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.
Intervention: biopsy (Procedure)
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.
Intervention: pharmacological study (Other)
Outcomes
Primary Outcomes
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
Acute toxicity graded by NCI/DCTDC Common Toxicity Criteria
Time Frame: Up to 24 hours
Late toxicity graded by NCI/DCTDC Common Toxicity Criteria
Time Frame: Up to 28 days
Dose-limiting toxicity defined as any grade III or higher toxicity
Time Frame: Up to 45 days
Acceptable signal-to-noise ratio (75 or above)
Time Frame: Up to 45 days
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
Secondary Outcomes
No secondary outcomes reported