AP5346 for Recurrent/Unresectable Squamous Cell Carcinoma of the Head and Neck: A Pilot Study With Clinical and Biological Endpoints
- Compare the delivered-dose of platinum per gram of wet weight from a single dose of
AP5346 vs a single dose of oxaliplatin in patients with metastatic and/or unresectable
recurrent squamous cell carcinoma of the head and neck (SCCHN).
- Correlate platinum accumulation in the tumor and tumor DNA with clinical response in
patients treated with these regimens.
- Correlate platinum accumulation in the tumor and tumor DNA with molecular tumor
response as determined by GADD153 expression in patients treated with these regimens.
- Quantify, by immunohistochemistry, the expression of the copper transporters CTR1,
ATP7A, and ATP7B in SCCHN tumors and correlate expression of these transporters with
tumor platinum levels.
- Determine response in patients treated with AP5346.
- Obtain additional data on the safety of AP5346 in these patients.
OUTLINE: This is a randomized, pilot study. Patients are randomized to 1 of 2 treatment
- Arm I: Patients receive AP5346 IV over 2 hours three times daily on days 1 and 15.
- Arm II: Patients receive a single dose of unmodified oxaliplatin IV over 2 hours on day
Beginning on day 29, all patients may receive AP5346 as in arm I. Treatment repeats every 28
days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor biopsy before and 24 hours after the first course of treatment for
correlative pharmacological, immunohistochemical (IHC), and molecular studies. Tumor
specimens are assessed for platinum content, GADD153 gene expression (by molecular
analysis), and copper transporter (CTR1, ATP7A, ATP7B) expression by IHC.
PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.
Allocation: Randomized, Primary Purpose: Treatment
Delivered-dose of platinum 24 hours after IV injection of a single dose of AP5346 vs a single dose of oxaliplatin
William L. Read, MD
University of California, San Diego
United States: Federal Government
|Moores UCSD Cancer Center||La Jolla, California 92093-0658|