A Phase II Study of Surgical Debulking With Peritonectomy and Biweekly Intraperitoneal 5FU With Systemic Oxaliplatin/5FU/Leucovorin in Patients With Pseudomyxoma Peritonei or Peritoneal Carcinomatosis

This study prospectively evaluates a multidisciplinary approach to patients with intraperitoneal carcinomatosis at Washington University. Patients with peritoneal carcinomatosis or pseudomyxoma peritonei will undergo debulking surgery with peritonectomy and placement of adhesive barrier film followed by repeated delayed intraperitoneal chemotherapy with 5FU with systemic oxaliplatin-based chemotherapy on a biweekly schedule. A retrospective review of patients treated in a similar manner at our institution showed good tolerance and efficacy. This formal Phase II study is planned to determine the safety, toxicities and survival of patients with peritoneal carcinomatosis and pseudomyxoma peritonei treated with this regimen.

Study Overview

• Status: Terminated
• Conditions: Peritoneal Neoplasms
• Intervention / Treatment: Drug: FOLFOX; Procedure: Surgical debulking with peritonectomy; Drug: Intraperitoneal 5FU

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Eligibility Criteria:

• Histological Diagnosis: Patients must have a histologically documented pseudomyxoma peritonei or peritoneal carcinomatosis from colorectal/appendiceal and small intestinal adenocarcinoma.
• Patients may have prior chemotherapy.
• Age: Patients must be greater than or equal to 18 years old. Because no dosing or toxicity data are currently available on the use of oxaliplatin in patients <18 years of age, children are excluded from this study, but will be eligible for other pediatric Phase I single-agent trials, when available.
• Performance Status: ECOG 0-2.
• Life Expectancy: greater than 8 weeks.
• Recovery from Intercurrent Illness: Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
• Hematological Status: Patients must have adequate bone marrow function defined as an absolute neutrophil count greater than or equal to 1,500/mm3, platelet count greater than or equal to 100,000/mm3 and hemoglobin greater than or equal to 8 g/dl.
• Hepatic Function: Total bilirubin must be less than or equal to institutional upper limit of normal (ULN). Transaminases (SGOT and/or SGPT) may be up to 2.5 X ULN if alkaline phosphatase is less than or equal to ULN, or alkaline phosphatase may be up to 4 x ULN if transaminases are less than or equal to ULN. However, patients who have both transaminase elevation greater than 1.5 x ULN and alkaline phosphatase greater than 2.5 x ULN are not eligible for the study.
• Renal Function: Patients must have adequate renal function defined as serum creatinine less than or equal to 2.0 mg/dl or creatinine clearance greater than or equal to 60 ml/min/1.73 m2 for patients with creatinine levels above 2.0 mg/dl.
• Sexually Active Patients: For all sexually active patients, the use of adequate barrier contraception (hormonal or barrier method of birth control) will be required during therapy, prior to study entry and for the duration of study participation. Non-pregnant status will be determined in all women of childbearing potential. Pregnant and nursing women patients are not eligible.
• HIV-Positive Patients: Patients receiving anti-retroviral therapy (HAART) for HIV infection are excluded from the study because of possible pharmacokinetic interactions. Appropriate studies will be undertaken in patients receiving HAART therapy, when indicated.
• Informed Consent: After being informed of the treatment involved, patients must give written consent. The patient should not have any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.
• Inclusion of Women and Minorities: Entry to this study is open to both men and women and to all racial and ethnic subgroups.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Peritonectomy + IP5FU + FOLFOX; Surgical debulking with peritonectomy; IP 5FU 600 mg/m^2 over 30-60 minutes with patient rotating every 15 minutes. Repeated every 2 weeks for a total of 9 cycles.; FOLFOX (oxaliplatin, 5FU, leucovorin) will follow IP therapy. Oxaliplatin 85 mg/m^2 over 2 hours with leucovorin at 400 mg/m^2 and IV 5-FU at 2400 mg/m^2 over 46 hours. Repeated every 2 weeks for a total of 8 cycles.

Drug: FOLFOX; Other Names: Leucovorin; Oxaliplatin; Fluorouracil; Efudex; USAN; Procedure: Surgical debulking with peritonectomy; Drug: Intraperitoneal 5FU; Other Names: Fluorouracil; Efudex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability of the Planned Treatment Regimen as Measured by Number of Participants With Grade 3 or Higher Adverse Events	30 days after end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Rate	-Progressive disease - at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.	Median follow-up was 32 months
Number of Participants Who Experience Surgical Complications Associated With This Regimen		Median follow-up was 32 months
Progression-free Survival		Median follow-up was 32 months
Overall Survival		Median follow-up was 32 months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: James Fleshman, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: July 14, 2006
• First Submitted That Met QC Criteria: July 14, 2006
• First Posted (Estimate): July 17, 2006

Study Record Updates

• Last Update Posted (Estimate): December 13, 2016
• Last Update Submitted That Met QC Criteria: October 19, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Digestive System Neoplasms; Abdominal Neoplasms; Neoplasms, Cystic, Mucinous, and Serous; Adenocarcinoma, Mucinous; Carcinoma; Peritoneal Neoplasms; Pseudomyxoma Peritonei; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin
• Other Study ID Numbers: 06-0312