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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
47

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Overall response rates
Time Frame: 12 months
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Royal Marsden NHS Foundation Trust

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Roche Pharma AG

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 23, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 30, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 1, 2009

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 25, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 23, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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