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

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ClinicalTrials.gov Identifier: NCT01022541
Recruitment Status : Completed
First Posted : December 1, 2009
Last Update Posted : November 25, 2015
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Capecitabine Drug: Oxaliplatin Drug: Bevacizumab Procedure: Liver metastasectomy Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2006
Actual Primary Completion Date : December 2010
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
This is a single arm study
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 Name: 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 Name: 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 Name: 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).




Primary Outcome Measures :
  1. Overall response rates [ Time Frame: 12 months ]

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


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01022541


Locations
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United Kingdom
David Cunningham
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Roche Pharma AG
Investigators
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Principal Investigator: David Cunningham Royal Marsden NHS Foundation Trust

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01022541     History of Changes
Obsolete Identifiers: NCT00450346
Other Study ID Numbers: 2676
First Posted: December 1, 2009    Key Record Dates
Last Update Posted: November 25, 2015
Last Verified: May 2013
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Capecitabine
Oxaliplatin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action