Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer
- Conditions
- Carcinoma of the AppendixColorectal CancerPrimary Peritoneal Cavity Cancer
- Interventions
- Registration Number
- NCT00458809
- Lead Sponsor
- Wake Forest University Health Sciences
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Adding chemotherapy to hyperthermia and infusing it directly into the abdomen may kill more tumor cells. Giving this treatment after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase I trial is studying the side effects and best dose of intraperitoneal hyperthermic perfusion with oxaliplatin in treating patients with stage IV peritoneal cancer due to appendix cancer or colorectal cancer.
- Detailed Description
OBJECTIVES:
* Determine the toxicity of intraperitoneal hyperthermic chemoperfusion with oxaliplatin in patients with stage IV peritoneal surface malignancies from primary colorectal or appendiceal cancer.
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 oxaliplatin Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 oxaliplatin Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2
- Primary Outcome Measures
Name Time Method Maximum tolerated dose 18 days 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)
- Secondary Outcome Measures
Name Time Method Pharmacokinetics day of surgery (day one) Evaluation of the pharmacokinetics of oxaliplatin in perfusate, normal peritoneum, and peritoneal surface tumors during intraperitoneal hyperthermic chemoperfusion
Change in the phenotypic expression of proteins involved in the apoptotic and heat-stress inducible pathways Day of surgery (day one) Analysis of the expression of proteins involved in the apoptotic and stress-inducible heat shock protein pathways before and after intraperitoneal hyperthermic chemoperfusion with oxaliplatin. These proteins shall include cellular levels of Fas and TRAIL, components of the DISC (FADD, TRADD, FLIP, and Caspase 8), mitochondrial proteins (Bax, Bak, Bcl-2, and Bcl-XL), and the heat shock protein family (HSPs 27, 40, 70, and 90).
Trial Locations
- Locations (1)
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States