UPCC: 7597: PHASE I TRIAL OF EF5, AN AGENT FOR DETECTING HYPOXIA

University Of Pennsylvania, Philadelphia PA

Investigators

Linked publications & trials

Abstract

This is a Phase I/II trial of the 2-nitroimidazole drug, EF5, in patients with biopsy proven malignancies. EF5 is a drug which is being studied as a diagnostic agent for the detection of hypoxia in human tumors. 48 hours (range 40-55) prior to either surgical resection or biopsy of a soft tissue sarcoma/spindle cell neoplasm, cervical carcinoma or head/neck carcinoma, patients will receive EF5 through an intravenous injection at a rate of no greater than 350 ml/hr. At the time of surgical resection or biopsy via ultrasound guidance, multiple tumor pieces will be obtained and later assayed for the presence of EF5. Eppendorf needle electrode measurement of tumor oxygenation will be made in regions corresponding to biopsy sites. Using in vitro techniques, the signal to noise ratio EF5 binding (maximum tumor binding under hypoxic conditions to minimum binding in tissue) will be determined in the tumor biopsies. The starting dose for this trial will be 9 mg/kg based upon the results of preclinical studies. Six patients will be entered into each dose cohort and standard criteria will be used for dose escalation or de-escalation. Patients will be assessed clinically for toxicity based upon the NCI/DCTDC Common Toxicity Criteria. The optimal dose of EF5 will be defined as that dose which results in less than 2 instances of any grade III or higher toxicity among 6 consecutively treated patients and that dose which provides an optimal signal to noise ratio of 75 in biopsied tissue. A total of 10 patients will be treated at the optimal dose. The presence of hypoxia in human soft tissue sarcomas/spindle cell neoplasm, head and neck carcinoma and cervical carcinomas, based upon EF5 binding and Eppendorf needle electrod measurements, will be determined.