Clinical trial NCT00458809: Intraperitoneal Hyperthermic Perfusion With Oxaliplatin in Treating Patients With Stage IV Peritoneal Cancer Due to Appendix Cancer or Colorectal Cancer
Official title: A Phase I Evaluation of Intraperitoneal Hyperthermic Chemoperfusion With Oxaliplatin for Peritoneal Surface Disemmination of Appendiceal and Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma of the Appendix
Colorectal Cancer
Primary Peritoneal Cavity Cancer
Keywords: recurrent colon cancer
stage IV colon cancer
carcinoma of the appendix
recurrent rectal cancer
stage IV rectal cancer
primary peritoneal cavity cancer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

PRIOR CONCURRENT THERAPY:

* Recovered from prior surgery, radiotherapy, and other anticancer therapies
* More than 30 days since prior and no other concurrent investigational therapy
* No prior radiotherapy to \> 25% of bone marrow
* No prior allogeneic stem cell transplantation
* No concurrent antiretroviral therapy

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: 18 days
Secondary outcomes:
measure: Pharmacokinetics
timeFrame: day of surgery (day one)
measure: Change in the phenotypic expression of proteins involved in the apoptotic and heat-stress inducible pathways
timeFrame: Day of surgery (day one)
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: John H. Stewart, MD
role: STUDY_CHAIR
References:
citation: Stewart JH 4th, Shen P, Russell G, Fenstermaker J, McWilliams L, Coldrun FM, Levine KE, Jones BT, Levine EA. A phase I trial of oxaliplatin for intraperitoneal hyperthermic chemoperfusion for the treatment of peritoneal surface dissemination from colorectal and appendiceal cancers. Ann Surg Oncol. 2008 Aug;15(8):2137-45. doi: 10.1245/s10434-008-9967-1. Epub 2008 May 21.