A Phase I Study of AFP464 (Aminoflavone Prodrug) in Patients With Advanced Solid Tumors
I. Determine the dose-limiting toxicity and maximum tolerated dose of AFP464 in patients
with advanced solid tumors.
II. Assess the safety and tolerability of this drug in these patients.
I. Observe clinical response in patients treated with this drug. II. Characterize the
pharmacokinetics of this drug in these patients. III. Determine the clinical significance of
genetic polymorphisms on the genes coding metabolizing enzymes (e.g., CYP1A1, 1A2, 2C9,
2C19, and SULTA1) and on the disposition and efficacy/toxicity of AFP464 and AF.
OUTLINE: This a dose-escalation, multicenter study.
Patients receive AFP464 IV over 3 hours on days 1, 8, and 15. Courses repeat every 28 days
in the absence of unacceptable toxicity or disease progression.
Cohorts of 2-6 patients receive escalating doses of AFP464 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose at which ≤ 1 of 6 patients experience
dose-limiting toxicity. An additional 10 patients whose tumor is amenable to biopsy are
treated at the MTD.
Patients undergo blood collection periodically for pharmacokinetic and pharmacodynamic
studies. Patients treated at the MTD also undergo tumor tissue biopsies periodically for
additional pharmacodynamic and correlative biomarker studies.
After completion of study treatment, patients are followed for 4 weeks.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose determined by dose-limiting toxicity
Wayne State University
United States: Food and Drug Administration
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