Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over Other USCTU-4351 EPOC, USCTU-EPOC, EUDRACT-2006-003121-82, ISRCTN22944367, EU-20732, NCT00482222

Objectives

Primary

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

Secondary

1. Compare the overall survival of patients treated with these regimens.
2. Compare the quality of life of patients treated with these regimens.
3. Compare the cost effectiveness of these regimens in these patients.

Entry Criteria

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

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

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

Expected Enrollment

Outcomes

Progression-free survival

Response rate before surgery as assessed by RECIST criteria
Pathological resection status
Overall survival
Toxicity
Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21
Cost effectiveness
Safety

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

Trial Contact Information

Trial Lead Organizations

Southampton General Hospital

John Primrose, MD, Protocol chair		Ph: 44-23-8079-6144 Email: j.n.primrose@soton.ac.uk

United Kingdom
England
	Basildon
	Basildon University Hospital
		Pauline Leonard, MD	Ph:  44-1702-435-555
	Basingstoke
	North Hampshire Hospital
		Charlotte Rees, MD	Ph:  44-125-631-4793
	Bournemouth
	Royal Bournemouth Hospital NHS Trust
		Tamas Hickish, MD	Ph:  44-1202-303-626
			Email: tamas.hickish@rbch.nhs.uk
	Cambridge
	Addenbrooke's Hospital
		Pippa Corrie, PhD, FRCP	Ph:  44-1223-274-401
			Email: pippa.corrie@addenbrookes.nhs.uk
	Guildford
	St. Luke's Cancer Centre at Royal Surrey County Hospital
		Sharadah Essapen, MD	Ph:  44-1483-571-122
	Liverpool
	Aintree University Hospital
		Graeme Poston, MD	Ph:  44-151-525-5980
			Email: graeme.poston@aintree.nhs.uk
	Royal Liverpool University Hospital
		Paula Ghaneh, MD
	London
	Charing Cross Hospital
		Charles Lowdell, MD, BSc, MBBS, FRCP, FRCR	Ph:  44-208-383-0576
			Email: charles.lowdell@imperial.nhs.uk
	Royal Marsden - London
		David Cunningham, MD	Ph:  44-20-8661-3156
	Saint Bartholomew's Hospital
		Sarah Slater, MD	Ph:  44-20-7601-8391
	UCL Cancer Institute
		Astrid Mayer, MD	Ph:  44-207-794-0500
			Email: a.mayer@ucl.ac.uk
	Merseyside
	Clatterbridge Centre for Oncology
		David Smith, MD	Ph:  44-151-334-1155
			Email: david.smith@ccotrust.nhs.uk
	Newport
	St. Mary's Hospital
		Christopher Baughan, MD	Ph:  44-1983-524-081
	Nottingham
	Cancer Research Centre at Weston Park Hospital
		J. Hornbuckle, MD	Ph:  44-115-969-1169 ext. 47599
	Poole Dorset
	Poole Hospital NHS Trust
		Tamas Hickish, MD	Ph:  44-1202-448-263
	Salisbury
	Salisbury District Hospital
		Tim Iveson, MD	Ph:  44-1722-336-262 ext. 4688
	Southampton
	Southampton General Hospital
		John Primrose, MD	Ph:  44-23-8079-6144
			Email: j.n.primrose@soton.ac.uk
	Sutton
	Royal Marsden - Surrey
		David Cunningham, MD	Ph:  44-20-8661-3279
			Email: david.cunningham@rmh.nhs.uk
	Westcliff-On-Sea
	Southend University Hospital NHS Foundation Trust
		Pauline Leonard, MD	Ph:  44-1702-435-555
	Worthing
	Worthing Hospital
		Andrew Webb, MD	Ph:  44-1903-205-111
Wales
	Cardiff
	University Hospital of Wales
		Timothy Maughan, MD	Ph:  44-2920-316-904
	Velindre Cancer Center at Velindre Hospital
		Timothy Maughan, MD	Ph:  44-2920-316-904

Registry Information
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
Trial Start Date		2007-02-05
Trial Completion Date		2014-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00482222
Date Submitted to PDQ		2007-05-07
Information Last Verified		2008-04-06