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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT00458809
First received: April 9, 2007
Last updated: April 26, 2012
Last verified: April 2012
  Purpose

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 Intervention Phase
Carcinoma of the Appendix
Colorectal Cancer
Primary Peritoneal Cavity Cancer
Drug: oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • Maximum tolerated dose [ Time Frame: 18 days ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: day of surgery (day one) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day of surgery (day one) ] [ Designated as safety issue: No ]
    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).


Enrollment: 16
Study Start Date: March 2007
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00458809

Locations
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Study Chair: John H. Stewart, MD Comprehensive Cancer Center of Wake Forest University
  More Information

Additional Information:
Publications:
Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT00458809     History of Changes
Other Study ID Numbers: CDR0000540283, P30CA012197, CCCWFU-59106, CCCWFU-IRB00000847, CCCWFU-59106 IPHC
Study First Received: April 9, 2007
Last Updated: April 26, 2012
Health Authority: United States: Federal Government

Keywords provided by Comprehensive Cancer Center of Wake Forest University:
recurrent colon cancer
stage IV colon cancer
carcinoma of the appendix
recurrent rectal cancer
stage IV rectal cancer
primary peritoneal cavity cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Peritoneal Neoplasms
Fever
Carcinoma
Appendiceal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Abdominal Neoplasms
Peritoneal Diseases
Body Temperature Changes
Signs and Symptoms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Cecal Neoplasms
Cecal Diseases
Oxaliplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014