PERIOPERATIVE TREATMENT WITH COI-B (CAPECITABINE, OXALIPLATIN, IRINOTECAN AND BEVACIZUMAB) OF HIGH RISK OR BORDERLINE RESECTABLE COLORECTAL CANCER LIVER METASTASES (COI-B)

August 6, 2019 updated by: Filippo Pietrantonio, M.D., Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Capecitabine, oxaliplatin, irinotecan and bevacizumab as perioperative strategy of borderline and/or high risk resectable colorectal cancer liver metastases

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Previous studies demonstrated a significant association between tumor regression grade of hepatic colorectal metastases (TRG1: complete pathological response; TRG2: major pathological response; TRG3: partial pathological response; versus TRG4-5 no pathological response) and outcome in terms of survival after neoadjuvant treatment. In particular, retrospective data showed an association between oxaliplatin-based chemotherapy and improvement of grade and percentage of tumor regression; moreover, the addition of Bevacizumab seems to improve TRG over chemotherapy alone, conferring also a protection against liver damage due to chemotherapy-induced sinusoidal obstruction syndrome.

This is the rationale that induced us to carry out an evaluation and feasibility assessment of a perioperative approach with COI-B regimen in patients affected by high risk or borderline resectable colorectal liver metastases, with or without previous resection of primary tumor.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Mi
      • Milan, Mi, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale Tumori

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Inclusion criteria:

  • Histological diagnosis of colorectal adenocarcinoma.
  • Liver-limited metastases or metastases mainly (≥80% total disease burden) limited to the liver with extrahepatic disease judged resectable concomitantly or sequentially. Primary tumor may be resected or not, but patient must not be symptomatic for T.
  • Previous adjuvant therapy is allowed if it had been terminated for at least 6 months.
  • Previous first line treatment (irinotecan or oxaliplatin containing regimen) with stable or partial response after no more than 3 months of treatment
  • Age >= 18 years
  • Performance Status (ECOG <2)
  • Adequate organ function including the following:
  • Adequate bone marrow reserve: WBC count >3.0x109/L, absolute neutrophil count >1.5x109/L, platelet count >100x109/L, and hemoglobin >10 g/dL .
  • Hepatic: bilirubin < 1.5 times the ULN, alkaline phosphatase, aspartate transaminase, and alanine transaminase < 2.5 xULN
  • Renal : serum creatinin <2.0xULN
  • Patients compliance and geographic proximity that allows for adequate follow-up
  • Patients must sign an informed consent document (ICD)
  • Male and female patients with reproductive potential must use an approved contraceptive method.

Exclusion Criteria:

  • Tumor involvement of liver > 75%
  • Chance of a liver remnant after surgery < 25%
  • Eligibility for concurrent radiotherapeutic treatment
  • Disease progression during first line chemotherapy with FOLFOX, XELOX, FOLFIRI or XELIRI plus bevacizumab
  • Previous treatment with more than 3 months of FOLFOX or FOLFIRI
  • Previous therapy with bevacizumab or cetuximab or panitumumab
  • Administration of other experimental drugs during the study.
  • Body Mass Index > 35
  • Brain metastases.
  • Pregnancy and breast-feeding.
  • Serious or uncontrolled medical pathologies or active infections that would jeopardize the possibility of receiving the investigated treatment. Disorders that could influence the absorption of capecitabine (e.g. malabsorption), intestinal occlusion, Crohn's disease or ulcerative colitis.
  • Psychiatric disorders, neurologic disease or other conditions that would make it impossible to comply with the protocol procedures. Peripheral neuropathy not related to oxaliplatin previous administration.
  • Previous dangerous life threatening toxicities from fluoropyrimidine.
  • Positive anamnesis with regard to other neoplastic diseases except for the ones that have been cured for more than 5 years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: open label
Single arm, open label
Drug: capecitabine, oxaliplatin, irinotecan and bevacizumab
perioperative COI-B

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological response rate
Time Frame: Assessed at the time of surgery of liver metastases (between weeks 17-20 from enrollment)

Primary:

- To evaluate the activity of the regimen with regards to major/complete pathological response. Major/complete pathological response is measured by pathologist in terms of tumor regression grade (TRG) as described by Rubbia-Brandt L, Annals of Oncology 2007 (percentage of vial residual cells 0-10%).
Assessed at the time of surgery of liver metastases (between weeks 17-20 from enrollment)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
RECIST Response rate
Time Frame: Available at week 9 after enrollment
- Response rate according to RECIST vers. 1.1 criteria
Available at week 9 after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

  • Principal Investigator: Filippo de Braud, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2013

Primary Completion (Actual)

March 30, 2017

Study Completion (Actual)

March 30, 2017

Study Registration Dates

First Submitted

December 20, 2013

First Submitted That Met QC Criteria

March 11, 2014

First Posted (Estimate)

March 13, 2014

Study Record Updates

Last Update Posted (Actual)

August 7, 2019

Last Update Submitted That Met QC Criteria

August 6, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COI-B

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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