Combination Chemotherapy With or Without Cetuximab Before and After Surgery in Treating Patients With Resectable Liver Metastases Caused By Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title:

A Prospective Randomised Open Label Trial of Oxaliplatin/Fluoropyrimidine Versus Oxaliplatin/Fluoropyrimidine Plus Cetuximab Pre and Post Operatively in Patients With Resectable Colorectal Liver Metastasis Requiring Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00482222
• Other study ID #: CDR0000549541
• Secondary ID: USCTU-4351USCTU-
• Status: Recruiting
• Phase: Phase 3
• First received: June 4, 2007
• Last updated: January 22, 2013
• Start date: February 2007

Study information

• Verified date: April 2008
• Source: University of Southampton
• Contact: Louisa Little
• Phone: 02380795154
• Is FDA regulated: No
• Health authority: UK: Medicines and Healthcare producets Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy together with monoclonal antibodies before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without cetuximab in treating liver metastases caused by colorectal cancer.

PURPOSE: This randomized phase III trial is studying combination chemotherapy to compare how well it works when given with or without cetuximab before and after surgery in treating patients with resectable liver metastases caused by colorectal cancer.

Description:

OBJECTIVES:

Primary

• Compare progression-free survival of patients with resectable colorectal liver metastases treated with neoadjuvant and adjuvant combination chemotherapy with vs without cetuximab.

Secondary

• Compare the overall survival of patients treated with these regimens.

• Compare the quality of life of patients treated with these regimens.

• Compare the cost effectiveness of these regimens in these patients.

OUTLINE: This is a prospective, randomized, multicenter, open-label study. Patients are stratified according to participating center and assigned chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms.

• Neoadjuvant therapy:

• Arm I: Patients receive 1 of the following chemotherapy regimens:

• OxMdG: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

• CAPOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive 1 of the following regimens:

• OxMdG + cetuximab: Patients receive cetuximab IV over 1-2 hours on day 1 and OxMdG chemotherapy as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

• CAPOX + cetuximab: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and CAPOX chemotherapy as in arm I. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

• Surgery: Beginning 2-6 weeks after completion of chemotherapy, patients in both arms undergo liver resection.

• Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive treatment (OxMdG or CAPOX with or without cetuximab) as in arm I or II of neoadjuvant therapy.

• Arm I: Treatment with OxMdG repeats every 2 weeks for up to 6 courses and treatment with CAPOX repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

• Arm II: Treatment with OxMdG + cetuximab repeats every 2 weeks for up to 6 courses and treatment with CAPOX + cetuximab repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, every 12 weeks during chemotherapy, at completion of study treatment, every 3 months for 1 year, and then every 6 months thereafter.

Cost per life year and per quality-adjusted life year is assessed at baseline, every 12 weeks during treatment, and then at 3, 5, and 10 years.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 340
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically* or radiologically confirmed primary adenocarcinoma of the colon or rectum

• Advanced and/or metastatic disease NOTE: *Liver metastases should not be biopsied

• Must have potentially resectable liver metastases present, as defined by any of the following:

• Metachronous metastases AND complete resection of the primary tumor without gross or microscopic evidence of residual disease (R0)

• Synchronous metastases AND R0 resection of the primary tumor > 1 month before study entry

• Synchronous metastases with sufficient evidence (e.g., by CT scan or diagnostic laparoscopy) that both the primary tumor and the liver metastases can be completely resected during the same procedure and resection of primary tumor can be delayed for 3-4 months

• Suboptimally resectable disease (i.e., potentially resectable disease with compromise of the resection margins)

• No detectable extrahepatic tumor that cannot be completely resected

• Unidimensionally measurable disease

• No brain metastases

PATIENT CHARACTERISTICS:

• WHO performance status 0-2

• WBC = 4,000/mm³

• ANC = 1,500/mm³

• Platelet count > 150,000/mm³

• Bilirubin = 1.25 times upper limit of normal (ULN)

• Alkaline phosphatase = 5 times ULN

• AST or ALT = 3 times ULN

• Creatinine clearance > 50 mL/min OR glomerular filtration rate > 50 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for = 3 months after completion of study treatment

• No psychiatric or neurological condition that would preclude study compliance

• No partial or complete bowel obstruction

• No preexisting neuropathy > grade 1

• No other prior or concurrent malignant disease that, in the opinion of the investigator, would preclude study treatment

• No concurrent severe uncontrolled medical illness (including poorly-controlled angina or myocardial infarction within the past 3 months) that would preclude study treatment

• No known hypersensitivity reaction to any of the components of the study drugs

PRIOR CONCURRENT THERAPY:

• No prior systemic chemotherapy for metastatic disease

• More than 6 months since prior adjuvant chemotherapy comprising fluorouracil, leucovorin calcium, capecitabine, or irinotecan hydrochloride

• More than 1 month since prior rectal chemoradiotherapy comprising fluorouracil and leucovorin calcium

• No concurrent contraindicated medication

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Biological:
• cetuximab

Drug:
• capecitabine

• fluorouracil

• leucovorin calcium

• oxaliplatin

Other:
• study of socioeconomic and demographic variables

Procedure:
• adjuvant therapy

• neoadjuvant therapy

• quality-of-life assessment

Locations

Country	Name	City	State
United Kingdom	Basildon University Hospital	Basildon	England
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Aintree University Hospital	Liverpool	England
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Royal Marsden - London	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	UCL Cancer Institute	London	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	St. Mary's Hospital	Newport	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Nottingham	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Salisbury District Hospital	Salisbury	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England
United Kingdom	Worthing Hospital	Worthing	England

Sponsors (2)

Lead Sponsor	Collaborator
University of Southampton	University Hospital Southampton NHS Foundation Trust.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		end of study	No
Secondary	Response rate before surgery as assessed by RECIST criteria		end of study	No
Secondary	Pathological resection status		end of study	No
Secondary	Overall survival		end of study	No
Secondary	Toxicity		end of study	Yes
Secondary	Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21		end of study	No
Secondary	Cost effectiveness		end of study	No
Secondary	Safety		end of study	Yes