AP5346 or Oxaliplatin in Treating Patients With Metastatic and/or Unresectable Recurrent Head and Neck Cancer
RATIONALE: Drugs used in chemotherapy, such as AP5346 and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This randomized clinical trial is studying the dose of AP5346 to see how well it works compared with the dose of oxaliplatin in treating patients with metastatic and/or unresectable recurrent head and neck cancer.
Head and Neck Cancer
Drug: DACH polymer platinate AP5346
Genetic: gene expression analysis
Other: immunohistochemistry staining method
Other: pharmacological study
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||AP5346 for Recurrent/Unresectable Squamous Cell Carcinoma of the Head and Neck: A Pilot Study With Clinical and Biological Endpoints|
- Delivered-dose of platinum 24 hours after IV injection of a single dose of AP5346 vs a single dose of oxaliplatin [ Designated as safety issue: No ]
- Correlation of platinum accumulation in the tumor and tumor DNA with clinical response [ Designated as safety issue: No ]
- Correlation of platinum accumulation in the tumor and tumor DNA with molecular response as determined by GADD153 expression [ Designated as safety issue: No ]
- Quantification of expression of CTR1, ATP7A, and ATP7B in squamous cell carcinoma of the head and neck (SCCHN) tumors by immunohistochemistry [ Designated as safety issue: No ]
- Correlation of expression of CTR1, ATP7A, and ATP7B in SCCHN tumors with tumor platinum levels [ Designated as safety issue: No ]
- Toxicity of AP5346 [ Designated as safety issue: Yes ]
|Study Start Date:||May 2006|
- 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 arms.
- 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 1.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00415298
|United States, California|
|Moores UCSD Cancer Center|
|La Jolla, California, United States, 92093-0658|
|Study Chair:||William L. Read, MD||University of California, San Diego|