Capecitabine and Oxaliplatin Plus Bevacizumab as Neoadjuvant Treatment for Untreated Unresectable Liver-only Metastases From Colorectal Cancer

November 23, 2015 updated by: Royal Marsden NHS Foundation Trust

Phase II Clinical Trial of Capecitabine and Oxaliplatin Plus Bevacizumab as Neoadjuvant Treatment for Patients With Previously Untreated Unresectable Liver-only Metastases From Colorectal Cancer

To evaluate the overall response rate of patients with previously untreated unresectable liver-only metastases from colorectal cancer treated with neoadjuvant capecitabine and oxaliplatin plus bevacizumab.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

No previous treatment.

The 21 day cycle of treatment will be given for four courses before being reassessed by MRI/CT for resectability of their liver metastases.

Those patients with stable disease or partial response, but are not yet resectable will continue for a further four courses of treatment before reassessment.

Patients whose liver metastases have become resectable will proceed to surgery after a 6 week break from the last administration of Capecitabine (8 weeks from the last administration of Bevacizumab).

A further four courses of treatment will be administered post-operatively to commence at least 8 weeks after surgery and when the patient is well recovered and healed.

Study Type

Interventional

Enrollment (Actual)

47

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

  • United Kingdom
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • David Cunningham

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:

  • Histologically proven diagnosis of colorectal adenocarcinoma
  • Metastatic disease present in the liver only.
  • Absence of extrahepatic metastases excluded by CT chest, abdomen and pelvis. Indeterminate CT findings may require verification by FDG-PET scanning.
  • Liver-only metastases determined to be unresectable at presentation on a pre-treatment liver MRI with an appropriate liver specific contrast (eg. TESLA) by a specialist multidisciplinary team (consisting of medical oncologist, hepatic surgeon and radiologist). Guidelines for determining unresectability include:
  • presence of >4 metastases;
  • size >5cm;
  • location and distribution of metastatic disease within the liver unsuitable for resection with clear margins (eg. Involvement of both lobes of liver; invasion of intrahepatic vascular structures);
  • extent of liver involvement precluding resection with adequate post-resection residual liver parenchyma volume for viable liver function in the immediate post-operative period;
  • inability to retain adequate vascular in flow and out flow to maintain viable liver function.
  • No previous treatment for metastatic colorectal cancer, including chemotherapy, targeted or experimental therapies (e.g. anti-VEGF or anti-EGFR), radiotherapy to the liver, or surgery or radiofrequency ablation to liver metastases.
  • Feasibility of surgery with curative intent:
  • If the primary colorectal tumour is in situ, the primary tumour must also be resectable with curative intent
  • Patients presenting with liver metastases only relapse after initially curative resection of their primary colorectal cancer followed by treatment with adjuvant chemotherapy may not be entered into the study if the relapse has occurred within 12 months of completion of adjuvant treatment
  • Adequate medical fitness to undergo neoadjuvant treatment and surgery with curative intent (hepatectomy +/- resection of primary tumour, if required)
  • Absence of pre-existing liver dysfunction of Childs Pugh Grade B or greater. Patients who are suspected of having pre-existing liver dysfunction due to clinical, biochemical or radiological findings, should have significant liver disease excluded by a liver biopsy prior to study entry.

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: This is a single arm study
Drug: Capecitabine

Capecitabine 1700mg/m2/day in two divided doses to be administered orally for 14 days followed by 7 days rest. For 4 courses initially.

(For patients aged 75+ 1300mg/m2/day in two divided doses or 650mg/m2 twice daily)

Courses as per detailed description above.

Other Names:
  • Xeloda
Drug: Oxaliplatin

Oxaliplatin 130mg/m2 diluted in 5% dextrose will be given as an i.v. infusion over 2 hours. This will be administered on day 1 after bevacizumab. For 4 courses.

(Patients aged 75+ should receive oxaliplatin at a reduced dose i.e. 100mg/m2)

Courses as per detailed description above.

Other Names:
  • Eloxatin
Drug: Bevacizumab

Bevacizumab at a dose of 7.5 mg/kg, diluted in normal saline, will be administered as an iv infusion over 30 to 90 minutes before the administration of oxaliplatin on day 1 of every cycle.

The first infusion should be administered over 90 minutes. If well tolerated, the second infusion can be administered over 60 minutes. Provided that this is tolerated subsequent infusions can be administered over 30 minutes. If a patient experiences an infusion related adverse event with the 60 minute infusion, all subsequent infusions will be administered over 90 minutes. If a patient experiences an infusion related reaction with the 30 minute infusion, all subsequent infusions will be administered over 60 minutes

Courses as per detailed description above.

Other Names:
  • Avastin
Procedure: Liver metastasectomy
Patients with liver metastases which have become resectable and in whom surgery is still deemed appropriate should proceed to surgery after a 6 week interval from the last administration of capecitabine chemotherapy (at least 8 weeks from last administration of bevacizumab).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Overall response rates
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Complete resection (R0) rate
Time Frame: 12 months
12 months
Safety and feasibility of adding bevacizumab to neoadjuvant capecitabine and oxaliplatin in patients undergoing liver metastasectomy
Time Frame: 12 months
12 months
Other parameters of efficacy (response and survival) in patients with unresectable liver-only metastases treated with this neoadjuvant combination
Time Frame: 5 years
5 years

Collaborators and Investigators

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

Sponsor

Royal Marsden NHS Foundation Trust

Collaborators

Roche Pharma AG

Investigators

  • Principal Investigator: David Cunningham, Royal Marsden NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

June 1, 2006

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

February 1, 2015

Study Registration Dates

First Submitted

January 23, 2006

First Submitted That Met QC Criteria

November 30, 2009

First Posted (Estimate)

December 1, 2009

Study Record Updates

Last Update Posted (Estimate)

November 25, 2015

Last Update Submitted That Met QC Criteria

November 23, 2015

Last Verified

May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2676

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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