Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT00458809

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma of the Appendix Colorectal Cancer Primary Peritoneal Cavity Cancer	Drug: oxaliplatin	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Evaluation of Intraperitoneal Hyperthermic Chemoperfusion With Oxaliplatin for Peritoneal Surface Disemmination of Appendiceal and Colorectal Cancer

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Nov 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2 Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2	Drug: oxaliplatin Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin
Experimental: Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2 Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2	Drug: oxaliplatin Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin

Arm

Intervention/Treatment

Experimental: Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2

Drug: oxaliplatin

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin

Experimental: Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2

Drug: oxaliplatin

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin

Outcome Measures

Primary Outcome Measures

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

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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed colorectal or appendiceal cancer
Stage IV disease
Peritoneal surface dissemination of disease (peritoneal carcinomatosis)
Measurable disease according to RECIST criteria
No active CNS metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
Bilirubin ≤ 1.5 mg/dL
Alkaline phosphatase ≤ 3 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
No active infection or fever ≥ 101.3°F within the past 3 days
No other malignancy within the past 5 years except curatively treated basal cell skin cancer, cervical intra-epithelial neoplasia, or localized prostate cancer with a current prostate-specific antigen of < 1.0 mg/dL on 2 successive evaluations, ≥ 3 months apart, with the last evaluation within the past 4 weeks
No peripheral neuropathy ≥ grade 2
No other medical condition, mental illness, or substance abuse that, in the opinion of the principal investigator, would preclude study compliance
No known hypersensitivity to any component of oxaliplatin
No known HIV positivity
No hepatitis B or C positivity (active, previously treated, or both)
Not pregnant or nursing
Negative pregnancy test
Fertile patients and their partners must use effective contraception during and for 90 days after completion of study treatment