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

NCT01022541 | Completed Phase 2 DMC

• 1 other identifier: 2676
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rates

  12 months

Secondary Outcomes (3)

• Complete resection (R0) rate

  12 months

• Safety and feasibility of adding bevacizumab to neoadjuvant capecitabine and oxaliplatin in patients undergoing liver metastasectomy

  12 months

• Other parameters of efficacy (response and survival) in patients with unresectable liver-only metastases treated with this neoadjuvant combination

  5 years

Study Arms (1)

This is a single arm study

OTHER

This is a single arm study

Drug: Capecitabine; Drug: Oxaliplatin; Drug: Bevacizumab; Procedure: Liver metastasectomy

Interventions

Capecitabine DRUG

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.

Also known as: Xeloda

This is a single arm study

Oxaliplatin DRUG

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.

Also known as: Eloxatin

This is a single arm study

Bevacizumab DRUG

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.

Also known as: Avastin

This is a single arm study

Liver metastasectomy PROCEDURE

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).

This is a single arm study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Royal Marsden NHS Foundation Trust: lead
• Roche Pharma AG: collaborator

Study Sites (1)

David Cunningham

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Wong R, Cunningham D, Barbachano Y, Saffery C, Valle J, Hickish T, Mudan S, Brown G, Khan A, Wotherspoon A, Strimpakos AS, Thomas J, Compton S, Chua YJ, Chau I. A multicentre study of capecitabine, oxaliplatin plus bevacizumab as perioperative treatment of patients with poor-risk colorectal liver-only metastases not selected for upfront resection. Ann Oncol. 2011 Sep;22(9):2042-2048. doi: 10.1093/annonc/mdq714. Epub 2011 Feb 1.

  PMID: 21285134 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Capecitabine; Oxaliplatin; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Cunningham

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2006
• First Posted: December 1, 2009
• Study Start: June 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: February 1, 2015
• Last Updated: November 25, 2015

Record last verified: 2013-05

Locations

GB (1)