Hyperthermic Intraperitoneal Oxaliplatin for Peritoneal Malignancies

NCT ID: NCT00625092

Last Updated: 2017-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

17 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-10-31

Study Completion Date

2011-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Peritoneal Cavity Cancer

Keywords

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peritoneal cavity cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Hyperthermic Treatment

Patients receiving combination of hyperthermic intraperitoneal chemotherapy (HIPC) with oxaliplatin plus intraperitoneal 5-Fu and intraperitoneal leucovorin with peritoneal metastases.

Group Type EXPERIMENTAL

fluorouracil

Intervention Type DRUG

Post-operative day 1 and day 2, 600mg/m\^2 intraperitoneal (IP) held for 23 hours

leucovorin calcium

Intervention Type DRUG

Day 0 200 mg/m\^2 intraperitoneal held for 2 hours

oxaliplatin

Intervention Type DRUG

Day 0 hyperthermic intraperitoneal oxaliplatin held for 30 minutes - assigned dose level: Levels 1 through 7 - 300 to 600 mg/m\^2

cytoreductive surgery

Intervention Type PROCEDURE

Day 0 Cytoreductive surgery is a systematic attempt to remove all or nearly all peritoneal nodules.

Interventions

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fluorouracil

Post-operative day 1 and day 2, 600mg/m\^2 intraperitoneal (IP) held for 23 hours

Intervention Type DRUG

leucovorin calcium

Day 0 200 mg/m\^2 intraperitoneal held for 2 hours

Intervention Type DRUG

oxaliplatin

Day 0 hyperthermic intraperitoneal oxaliplatin held for 30 minutes - assigned dose level: Levels 1 through 7 - 300 to 600 mg/m\^2

Intervention Type DRUG

cytoreductive surgery

Day 0 Cytoreductive surgery is a systematic attempt to remove all or nearly all peritoneal nodules.

Intervention Type PROCEDURE

Other Intervention Names

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5-FU Eloxatin conventional surgery

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Todd M. Tuttle, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

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Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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0601M79448

Identifier Type: OTHER

Identifier Source: secondary_id

2005LS068

Identifier Type: -

Identifier Source: org_study_id