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

Phase 1
18 Years
Not Enrolling
Carcinoma of the Appendix, Colorectal Cancer, Primary Peritoneal Cavity Cancer

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Trial Information

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


- 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.

Inclusion Criteria


- 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


- 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


- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Description:

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)

Outcome Time Frame:

18 days

Safety Issue:


Principal Investigator

John H. Stewart, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Comprehensive Cancer Center of Wake Forest University


United States: Federal Government

Study ID:




Start Date:

March 2007

Completion Date:

Related Keywords:

  • Carcinoma of the Appendix
  • Colorectal Cancer
  • Primary Peritoneal Cavity Cancer
  • recurrent colon cancer
  • stage IV colon cancer
  • carcinoma of the appendix
  • recurrent rectal cancer
  • stage IV rectal cancer
  • primary peritoneal cavity cancer
  • Carcinoma
  • Colorectal Neoplasms
  • Fever
  • Peritoneal Neoplasms
  • Colonic Neoplasms



Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096