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

Primary Purpose

Carcinoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intraperitoneal Oxaliplatin
Bevacizumab
Capecitabine
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose Level 1

Dose Level 2

Dose Level 3

Dose Level 4

Dose Level 5

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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
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
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
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
Overall survival

Secondary Outcome Measures

Full Information

First Posted
February 1, 2010
Last Updated
November 10, 2022
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01061515
Brief Title
Biweekly Intraperitoneal Oxaliplatin With Systemic Capecitabine and Bevacizumab for Patients With Peritoneal Carcinomatosis From Appendiceal or Colorectal Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 10, 2011 (Actual)
Primary Completion Date
September 27, 2024 (Anticipated)
Study Completion Date
September 27, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Level 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Level 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Level 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Dose Level 5
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Intraperitoneal Oxaliplatin
Other Intervention Name(s)
Eloxatin
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Primary Outcome Measure Information:
Title
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
Time Frame
Completion of enrollment (approximately 8 years)
Title
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
Time Frame
30 days after completion of treatment (estimated to be 22 weeks)
Title
Progression rate
Description
-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
Time Frame
Through 4-12 weeks post-treatment (estimated to be 30 weeks)
Title
Progression-free survival (PFS)
Description
-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
Time Frame
Through completion of follow-up (estimated to be 5 years)
Title
Overall survival
Time Frame
Through completion of follow-up (estimated to be 5 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Tan, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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