Hyperthermic Intraperitoneal Oxaliplatin for Peritoneal Malignancies

Peritoneal Cavity Cancer Clinical Trial

Official title:

Phase I Hyperthermic Intraperitoneal Oxaliplatin for Peritoneal Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00625092
• Other study ID #: 2005LS068
• Secondary ID: 0601M79448
• Status: Completed
• Phase: Phase 1
• First received: February 27, 2008
• Last updated: November 27, 2017
• Start date: October 2007
• Est. completion date: September 2011

Study information

• Verified date: November 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fever
• Peritoneal Cavity Cancer
• Peritoneal Neoplasms

Intervention

Drug:
• fluorouracil
Post-operative day 1 and day 2, 600mg/m^2 intraperitoneal (IP) held for 23 hours
• leucovorin calcium
Day 0 200 mg/m^2 intraperitoneal held for 2 hours
• oxaliplatin
Day 0 hyperthermic intraperitoneal oxaliplatin held for 30 minutes - assigned dose level: Levels 1 through 7 - 300 to 600 mg/m^2

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

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of hyperthermic intraperitoneal oxaliplatin		30 Days Post Treatment
Secondary	Changes in quality-of-life	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.	Baseline and at 4, 8, and 12 months
Secondary	Overall survival		1 Year and 5 Years
Secondary	Time to Disease Progression		Monthly