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

NCT ID: NCT00458809

Last Updated: 2018-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2007-11-30

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.

Conditions

Carcinoma of the Appendix; Colorectal Cancer; Primary Peritoneal Cavity Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 200 mg/m2

Group Type: EXPERIMENTAL

oxaliplatin

Intervention Type: DRUG

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin

Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin 250 mg/m2

Group Type: EXPERIMENTAL

oxaliplatin

Intervention Type: DRUG

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin

Interventions

oxaliplatin

Intraperitoneal Hyperthermic Chemoperfusion with Oxaliplatin

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John H. Stewart, MD

Role: STUDY_CHAIR

Wake Forest University Health Sciences

Locations

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 18493824 (View on PubMed)

Other Identifiers

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CCCWFU-59106

Identifier Type: -

Identifier Source: secondary_id

CCCWFU-IRB00000847

Identifier Type: -

Identifier Source: secondary_id

CCCWFU-59106 IPHC

Identifier Type: -

Identifier Source: secondary_id

CDR0000540283

Identifier Type: -

Identifier Source: org_study_id