Biweekly Intraperitoneal Oxaliplatin With Systemic Capecitabine and Bevacizumab for Patients With Peritoneal Carcinomatosis From Appendiceal or Colorectal Cancer

A Phase I Dose-Escalation Trial of Biweekly Intraperitoneal Oxaliplatin With Systemic Capecitabine and Bevacizumab Following Cytoreduction in Patients With Peritoneal Carcinomatosis From Appendiceal or Colorectal Cancer

This study is to test escalating doses of intraperitoneal (IP) oxaliplatin in conjunction with systemic bevacizumab and capecitabine in patients with Peritoneal Carcinomatosis (PC) from either appendiceal or colorectal adenocarcinoma that have been adequately cytoreduced and have undergone a peritoneal scan demonstrating patency of at least one of the intraperitoneal ports that were placed at the time of debulking.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma
• Intervention / Treatment: Drug: Capecitabine; Drug: Bevacizumab; Drug: Intraperitoneal Oxaliplatin

Detailed Description

• To determine the maximum tolerated dose of IP oxaliplatin with systemic intravenous bevacizumab and oral capecitabine after adequate surgical debulking and peritoneal scan documenting function of intraperitoneal ports in patients with peritoneal carcinomatosis of appendiceal or colorectal etiology.
• To assess the safety and tolerability of repeated delayed intraperitoneal chemotherapy with oxaliplatin and systemic intravenous bevacizumab and oral capecitabine after adequate surgical debulking and peritoneal scan documenting function of intraperitoneal ports in patients with peritoneal carcinomatosis of appendiceal or colorectal etiology.
• To describe the progression rate, progression-free survival and overall survival in patients treated with this regimen.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

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

Description

Inclusion Criteria:

• Histological Diagnosis: Patients must have a histologically documented peritoneal carcinomatosis from either colorectal or appendiceal adenocarcinoma.
• Prior Surgical Debulking: Patients must have undergone debulking surgery with peritonectomy and have been allowed at least 4 weeks to recover prior to receiving chemotherapy.
• Port Placement: Intraperitoneal ports may be placed during or at any time separate from surgical debulking. Provided the patient has been allowed at least 4 weeks to recover from surgical debulking, no additional recovery time is required for port placement.
• Active port: Patients must undergo a peritoneal scan documenting at least one working intraperitoneal port prior to receiving chemotherapy.
• Patients may have received prior chemotherapy.
• Age: Patients must be ≥18 years of age. Because no dosing or toxicity data are currently available on the use of oxaliplatin in patients <18 years of age.
• Performance Status: (Eastern cooperativeOncology Group) ECOG 0-2.
• 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 arrhythmias.
• Informed Consent: All patients must be consented prior to chemotherapy. The patient should not have any serious medical of psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.

• Hematological Status:

  • absolute neutrophil count ≥1,500/mm³
  • platelet count ≥100,000/mm³
  • hemoglobin ≥8 g/dl.

• Hepatic function:

  • Total bilirubin must be <2X the institutional upper limit of normal (ULN)
  • Transaminases (SGOT and/or SGPT) must be ≤3X the institutional upper limit of normal (ULN)
  • Alkaline phosphatase must be ≤4X the institutional upper limit of normal (ULN)
• Renal Function: Patients must have adequate renal function prior to chemotherapy defined as serum creatinine ≤ 2.0 mg/dl or creatinine clearance ≥60 ml.min/1.73 m² for patients with creatinine levels above 2.0 mg/dl.

Exclusion Criteria:

• Pregnant or breast feeding: For all sexually active patients, the use of adequate 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.
• Prior history of hypersensitivity reactions to oxaliplatin, bevacizumab, 5-FU or capecitabine.
• Gastrointestinal ailments that may alter the absorption of oral medications (i.e. bowel obstruction, short-gut syndrome).
• Patients receiving antiretroviral therapy Highly Active Anti Retroviral Treatment (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.
• Patients with Grade 2 or higher peripheral neuropathy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1; Intraperitoneal oxaliplatin 25 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.	Drug: Capecitabine; Other Names: Xeloda; Drug: Bevacizumab; Other Names: Avastin; Drug: Intraperitoneal Oxaliplatin; Other Names: Eloxatin
Experimental: Dose Level 2; Intraperitoneal oxaliplatin 50 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.	Drug: Capecitabine; Other Names: Xeloda; Drug: Bevacizumab; Other Names: Avastin; Drug: Intraperitoneal Oxaliplatin; Other Names: Eloxatin
Experimental: Dose Level 3; Intraperitoneal oxaliplatin 65 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.	Drug: Capecitabine; Other Names: Xeloda; Drug: Bevacizumab; Other Names: Avastin; Drug: Intraperitoneal Oxaliplatin; Other Names: Eloxatin
Experimental: Dose Level 4; Intraperitoneal oxaliplatin 85 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.	Drug: Bevacizumab; Other Names: Avastin
Experimental: Dose Level 5; Intraperitoneal oxaliplatin 100 mg/m2 IP on day 1 of each cycle Bevacizumab 5 mg/kg CIVI on day 1 of each cycle Capecitabine PO BID on days 1-7 of each cycle. Each cycle is 14 days long.	Drug: Capecitabine; Other Names: Xeloda; Drug: Bevacizumab; Other Names: Avastin; Drug: Intraperitoneal Oxaliplatin; Other Names: Eloxatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the maximum tolerated dose of IP oxaliplatin with systemic intravenous bevacizumab and oral capecitabine after surgical debulking and peritoneal scan documenting functional of intraperitoneal ports in patients with peritoneal carcinomatosis		Completion of enrollment (approximately 8 years)
Assess the safety and tolerability of IP oxaliplatin and intravenous (i.v.) bevacizumab and oral capecitabine after surgical debulking and functional intraperitoneal ports in patients with peritoneal carcinomatosis of appendiceal or colorectal etiology		30 days after completion of treatment (estimated to be 22 weeks)
Progression rate	-Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions	Through 4-12 weeks post-treatment (estimated to be 30 weeks)
Progression-free survival (PFS)	-Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions	Through completion of follow-up (estimated to be 5 years)
Overall survival		Through completion of follow-up (estimated to be 5 years)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Benjamin Tan, 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 (Actual): May 10, 2011
• Primary Completion (Estimated): September 27, 2026
• Study Completion (Estimated): September 27, 2026

Study Registration Dates

• First Submitted: February 1, 2010
• First Submitted That Met QC Criteria: February 2, 2010
• First Posted (Estimated): February 3, 2010

Study Record Updates

• Last Update Posted (Estimated): September 17, 2025
• Last Update Submitted That Met QC Criteria: September 15, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: 10-0136 / 201107017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No