Hyperthermic Intraperitoneal Oxaliplatin for Peritoneal Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00625092
First received: February 27, 2008
Last updated: December 15, 2011
Last verified: December 2011
  Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, 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. Peritoneal infusion of heated and nonheated chemotherapy drugs after surgery may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of hyperthermic intraperitoneal oxaliplatin followed by intraperitoneal leucovorin and fluorouracil in treating patients with peritoneal cancer.


Condition Intervention Phase
Peritoneal Cavity Cancer
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Procedure: cytoreductive surgery
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Hyperthermic Intraperitoneal Oxaliplatin for Peritoneal Malignancies

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Maximum tolerated dose of hyperthermic intraperitoneal oxaliplatin [ Time Frame: 30 Days Post Treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes in quality-of-life [ Time Frame: Baseline and at 4, 8, and 12 months ] [ Designated as safety issue: No ]
    Using the Functional Assessment of Cancer Therapy for Colorectal Cancer (FACT-C) and SF-36 (Quality of Life Evaluation in Dialysis Patients) questionnaires, the quality of life following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPC) will be reported and compared to the preoperative baseline.

  • Overall survival [ Time Frame: 1 Year and 5 Years ] [ Designated as safety issue: No ]
  • Time to Disease Progression [ Time Frame: Monthly ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: October 2007
Study Completion Date: September 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hyperthermic Treatment
Patients receiving combination of hyperthermic intraperitoneal chemotherapy (HIPC) with oxaliplatin plus intraperitoneal 5-Fu and intraperitoneal leucovorin with peritoneal metastases.
Drug: fluorouracil
Post-operative day 1 and day 2, 600mg/m^2 intraperitoneal (IP) held for 23 hours
Other Name: 5-FU
Drug: leucovorin calcium
Day 0 200 mg/m^2 intraperitoneal held for 2 hours
Drug: oxaliplatin
Day 0 hyperthermic intraperitoneal oxaliplatin held for 30 minutes - assigned dose level: Levels 1 through 7 - 300 to 600 mg/m^2
Other Name: Eloxatin
Procedure: cytoreductive surgery
Day 0 Cytoreductive surgery is a systematic attempt to remove all or nearly all peritoneal nodules.
Other Name: conventional surgery

Detailed Description:

OBJECTIVES:

Primary

  • To determine the safety and optimal dose of hyperthermic intraperitoneal oxaliplatin when administered during cytoreductive surgery and followed by intraperitoneal leucovorin calcium and fluorouracil in patients with peritoneal malignancies.

Secondary

  • To determine the outcome of cytoreductive surgery in these patients.
  • To determine the time to disease progression and pattern of failure in patients treated with this regimen.
  • To determine the 1 and 5 year survival in patients treated with this regimen.
  • To compare quality-of-life pre- and post-surgery in these patients.
  • To characterize total- and free-platinum pharmacokinetics in the plasma and total platinum in the intraperitoneal space at baseline, during, and after hyperthermic intraperitoneal chemotherapy (HIPC).
  • To assess for the presence of genetic polymorphisms in the XDP and XRCC1 DNA repair genes.
  • To assess tumor and normal tissue concentrations for total platinum obtained at baseline and immediately after HIPC.

OUTLINE:

  • Cytoreductive Surgery: Patients undergo an exploratory laparotomy to remove all tumor nodules from all peritoneal surfaces prior to gastrointestinal anastomoses. An intraperitoneal drain is placed for postoperative intraperitoneal chemotherapy.
  • Hyperthermic peritoneal chemotherapy (HIPC): After cytoreductive surgery, but before intestinal anastomosis, patients receive oxaliplatin into the abdomen cavity at approximately 1 liter/min at 41-42º C and held for 30 minutes at the maximum tolerated dose. A heat exchanger maintains the fluid temperature at 44-46º C to maintain the intraperitoneal temperature at 41-42º C. Patients may receive fluid challenges, furosemide, mannitol, or renal dose dopamine to maintain a brisk diuresis at the discretion of the anesthesiologist.
  • Intraperitoneal chemotherapy: After HIPC, patients receive leucovorin calcium intraperitoneally through an intraperitoneal drain where it will remain for 2 hours and then drained. Patients then receive fluorouracil intraperitoneally through the intraperitoneal drain on day 1 and remain in the peritoneal fluid for 23 hours and then drained. The infusion will be repeated on day 2.

Blood samples are collected prior to surgery for pharmacogenetic studies and analyzed for the presence of genetic polymorphisms in the XPD and XRCC1 DNA repair genes and the GSTP1 and GSTM1 glutathione-S-transferase enzymes (i.e., XPD, Asp312Asn, XPD K751Q, XRCC1 Arg399GIn, XRCC1 Arg399Q, GSTP1 l105V, and GSTM1 DEL). Blood samples are also collected periodically for pharmacokinetic studies and analyzed for oxaliplatin concentrations. Normal and tumor tissue are collected periodically and analyzed for total platinum concentrations.

Quality of life is assessed at baseline and at 4, 8, and 12 months.

After completion of study treatment, patients are followed every 4 months for 2 years and then every 6 months for at least 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Patients must have histologic proof of peritoneal metastases (includes adenomucinosis)
  • Complete tumor resection possible (may include liver metastasis if treatable by resection or radiofrequency ablation)
  • Patients may have received previous chemotherapy (except peritoneal) and/or immunotherapy. If previous chemotherapy, at least 4 weeks must have passed since last dose.
  • Patients may have received previous radiation therapy, however radiation to the large bowel, small bowel and/or stomach will make the patient ineligible for this study.
  • Patients must have a Karnofsky performance score of ≥ 80%.
  • Adequate hematologic, renal and hepatic function within 14 days of registration defined as:

    • White blood count (WBC) ≥ 3,000
    • platelet count ≥ 70,000,
    • serum bilirubin ≤ 2.0 mg/dL,
    • serum creatinine ≤ 1.5 mg/dL
  • Patients must be at least 18 years of age
  • Patients must be able to provide informed consent

Exclusion criteria:

  • Metastatic disease is present outside the peritoneal cavity
  • Diagnosis of mesothelioma
  • Grade 2 or higher sensory neuropathy at time of study enrollment
  • History of allergic reaction to platinum compounds
  • Pregnant or lactating women. Pregnancy is a contraindication for receiving therapy, thus where relevant, patients will be required to use effective birth control. The agents used in this study include those which are pregnancy category D - clear evidence of risk in pregnancy. There is no information on the excretion of agents into breast milk therefore patients must refrain from breastfeeding while receiving study therapy.
  • Previous peritoneal chemotherapy.
  • Patients with uncontrolled concurrent medical problems (i.e. diabetes mellitus) or history of uncontrolled cardiovascular disease (no history of hospitalization for acute myocardial infarction or congestive heart failure (CHF) within 3 months prior to registration).
  • Patients have psychiatric or addictive disorders that preclude obtaining informed consent.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00625092

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Todd M. Tuttle, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00625092     History of Changes
Other Study ID Numbers: 2005LS068, 0601M79448
Study First Received: February 27, 2008
Last Updated: December 15, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
peritoneal cavity cancer

Additional relevant MeSH terms:
Neoplasms
Fever
Peritoneal Neoplasms
Body Temperature Changes
Signs and Symptoms
Abdominal Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on July 29, 2014