A Phase I Evaluation of Intraperitoneal Hyperthermic Chemoperfusion With Oxaliplatin for Peritoneal Surface Disemmination of Appendiceal and Colorectal Cancer
- Determine the toxicity of intraperitoneal hyperthermic chemoperfusion with oxaliplatin
in patients with stage IV peritoneal surface malignancies from primary colorectal or
- Determine the pharmacokinetics of this drug in perfusate, normal peritoneum, and
peritoneal surface tumors in these patients.
- Evaluate the expression of proteins involved in the apoptotic and stress-inducible heat
shock protein pathways (e.g., Fas, TRAIL, DISC components [FADD, TRADD, FLIP, and
caspase 8], mitochondrial proteins [Bax, Bak, Bcl-2, Bcl-X_L], and heat shock proteins
[HSPs 27, 40, 70 and 90]) before and after drug therapy.
OUTLINE: This is a nonrandomized, open-label, dose-escalation study.
Patients undergo gross tumor resection on day 1. After tumor debulking, patients receive
oxaliplatin over 2 hours by intraperitoneal hyperthermic chemotherapy (IPHC).
Cohorts of 3-6 patients in each stratum receive escalating doses of oxaliplatin until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are
treated at the MTD.
Patients undergo blood and tissue sampling before and after IPHC for pharmacokinetic studies
and for evaluation of proteins involved in apoptosis and heat-shock-mediated cell death
(e.g., Fas, TRAIL, FADD, TRADD, FLIP, caspase 8, Bax, Bak, Bcl-X, and heat shock proteins
27, 40, 70, and 90).
After completion of study treatment, patients are followed periodically for at least 1 year.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose
Maximum tolerated dose will be determined by the absence of dose limiting toxicites (serious adverse events related to Oxaplatin dosing within 18 days of administration)
John H. Stewart, MD
Comprehensive Cancer Center of Wake Forest University
United States: Federal Government
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|