Clinical trial NCT01022541: Capecitabine and Oxaliplatin Plus Bevacizumab as Neoadjuvant Treatment for Untreated Unresectable Liver-only Metastases From Colorectal Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2009-12-01
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Overall response rates
timeFrame: 12 months
Secondary outcomes:
measure: Complete resection (R0) rate
timeFrame: 12 months
measure: Safety and feasibility of adding bevacizumab to neoadjuvant capecitabine and oxaliplatin in patients undergoing liver metastasectomy
timeFrame: 12 months
measure: Other parameters of efficacy (response and survival) in patients with unresectable liver-only metastases treated with this neoadjuvant combination
timeFrame: 5 years
Other outcomes:
Locations:
city: Sutton
country: United Kingdom
facility: David Cunningham
state: Surrey
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: David Cunningham
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.