Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer
Condition: Carcinoma of the Appendix; Colorectal Cancer; Primary Peritoneal Cavity Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): oxaliplatin
Intervention type(s): Drug
Intervention description(s): Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin
Intervention MeSH terms: Oxaliplatin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent colon cancer; stage IV colon cancer; carcinoma of the appendix; recurrent rectal cancer; stage IV rectal cancer; primary peritoneal cavity cancer