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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01022541
• Other study ID #: 2676
• Status: Completed
• Phase: Phase 2
• First received: January 23, 2006
• Last updated: November 23, 2015
• Start date: June 2006
• Est. completion date: February 2015

Study information

• Verified date: May 2013
• Source: Royal Marsden NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00450346

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: February 2015
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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.
• 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.
• 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.

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).

Locations

Country	Name	City	State
United Kingdom	David Cunningham	Sutton	Surrey

Sponsors (2)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust	Roche Pharma AG

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rates		12 months	No
Secondary	Complete resection (R0) rate		12 months	No
Secondary	Safety and feasibility of adding bevacizumab to neoadjuvant capecitabine and oxaliplatin in patients undergoing liver metastasectomy		12 months	Yes
Secondary	Other parameters of efficacy (response and survival) in patients with unresectable liver-only metastases treated with this neoadjuvant combination		5 years	No