A Phase I Study and Pharmacological Trial of Once Weekly Aminoflavone Prodrug (AFP464) Administered 3 Out of Every 4 Weeks in Solid Tumor Patients
I. Determine the maximum tolerated dose (MTD) of AFP464 in patients with advanced solid
II. Evaluate the toxicity profile of AFP464. III. Characterize the plasma pharmacokinetics
and urinary excretion of AFP464 and aminoflavone in these patients.
IV. Identify any activity of AFP464 in patients with metastatic cancer. V. Explore whether
AFP464 induces CYP1A1 expression in tumor as measured by pre- and post-treatment tumor
biopsies at the MTD as well as in peripheral lymphocytes during the dose-escalation phase
and at the MTD.
VI. Explore the relationship between the pharmacogenetic analysis and toxicity or response.
OUTLINE: This is a dose-escalation study followed by an open-label study.
Patients receive AFP464 intravenously (IV) over 3 hours on days 1, 8, and 15. Treatment
repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 1-6 patients receive escalating doses of AFP464 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity. An additional 10 patients with accessible metastatic
breast, renal, or ovarian cancer receive AFP464 as above at the MTD. Blood, buccal cells,
and urine are collected before beginning treatment and during course 1 and examined for
biomarkers and biopharmacogenetics. Patients who are treated at the MTD also undergo
biopsies before and after course 1. Samples are analyzed via real time polymerase chain
reaction (RT-PCR) and immunofluorescence.
After completion of study treatment, patients are followed periodically for 3 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose, overall toxicity incidence, and toxicity profiles of AFP464 in the treatment of solid tumors
Measured by dose level and tumor site via the NCI CTCAE v 3.0. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|