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

Phase 2

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Capecitabine; Drug: Oxaliplatin; Drug: Bevacizumab; Procedure: Liver metastasectomy

• Registration Number: NCT01022541
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2006-01-23
• Study Start: 2006-06
• Study First Submitted QC: 2009-11-30
• Study First Posted: 2009-12-01
• Primary Completion: 2010-12
• Status Verified: 2013-05
• Study Completion: 2015-02
• Last Update Submitted: 2015-11-23
• Last Update Posted: 2015-11-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
This is a single arm study	Liver metastasectomy	This is a single arm study
This is a single arm study	Capecitabine	This is a single arm study
This is a single arm study	Oxaliplatin	This is a single arm study
This is a single arm study	Bevacizumab	This is a single arm study

Primary Outcome Measures

Name	Time	Method
Overall response rates	12 months

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

David Cunningham; 🇬🇧 Sutton, Surrey, United Kingdom