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

Alternate Title

Fluorouracil and Oxaliplatin With or Without Panitumumab In Treating Patients With High-Risk Colon Cancer That Can Be Removed by Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Biomarker/Laboratory analysis, Treatment Active Any age Other BCTU-FOXTROT-001 BCTU-FOxTROT-001, ISCRTN 87163246, EUDRACT 2007-001987-55, EU-20830, MREC-07/S0703/57, UKCRN 3771, NCT00647530

Objectives

Primary

1. To determine if neoadjuvant chemotherapy with or without panitumumab followed by deferred surgery and completion of chemotherapy postoperatively can reduce the 2-year recurrence as compared to surgery and postoperative chemotherapy with or without panitumumab.
2. To determine if adding panitumumab in the neoadjuvant treatment produces a measurable increase in antitumor efficacy as measured by tumor shrinkage.

Secondary

1. To assess the accuracy of pre-treatment CT scan staging.
2. To assess the tolerability of the neoadjuvant therapies.
3. To assess the nature and frequency of surgical complications.
4. To measure the impact of the treatments on quality of life and on resource usage.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the colon
  • Radiological T-staging of T4 or poor prognosis T3 (extramural depth > 5 mm)
  • Resectable disease



• Tumor not within 15 cm of the anal verge, as judged by sigmoidoscopy, or below the level of the sacral promontory, as judged by sagittal CT or MRI scan



• No concurrent obstruction and not previous defunctioning or stenting
  • Patients presenting with acute colonic obstruction may enter the trial only after successful defunctioning or stenting, and when recovered to a fitness level consistent with the other eligibility criteria



• No peritonitis secondary to perforated tumor



• No evidence of distant metastases or peritoneal or omental nodules (M1)

Prior/Concurrent Therapy:

• See Disease Characteristics
• No indication for radiotherapy

Patient Characteristics:

• WHO performance status 0-2
• Hemoglobin > 10.0 g/dL
• WBC > 3,000/mm³
• Platelets > 1000,000/mm³
• Bilirubin < 25 μmol/L
• Glomerular filtration rate > 50 mL/min
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months (females) 3 months (males) after completion of study therapy
• Able and willing to provide written informed consent for the study
• No serious medical comorbidity, including any of the following:
  • Uncontrolled inflammatory bowel disease
  • Uncontrolled angina or recent myocardial infarction (within the past 6 months)
  • Other serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery
• No other malignant disease within the past 5 years except for nonmelanoma skin cancer
• No history of interstitial pneumonitis or pulmonary fibrosis

Expected Enrollment

Outcomes

Recurrence or persistent disease (including failure of macroscopic disease clearance at primary surgery) within the first two years following randomization
Pathological down-staging as measured by depth of extramural spread among patients allocated to preoperative chemotherapy with or without panitumumab

Death from colon cancer
Overall survival
Pathological assessment of downstaging (involvement of lymph nodes, serosa, and resection margin) and quality of resection specimen
Radiological assessment of response to neoadjuvant treatment
Quality of life by EORTC QLQ C-30 and EuroQol EQ-5D
Health service costs
Surgical morbidity/mortality
Chemotherapy toxicity
Adverse events

Outline

This is a multicenter study. Patients are stratified according to age (< 50 year vs 50-59 years vs 60-69 years vs ≥ 70 years), radiological T-stage (T3 vs T4), radiological nodal status (Nx vs N0 vs N1 vs N2), site of primary tumor, proposed chemotherapy (OxMdG vs OxCap), and defunctioning colostomy (yes vs no).

Patients receive 1 of the 2 following treatment regimens:

• OxMdG: Patients receive oxaliplatin IV and folinic acid IV over 2 hours followed by fluorouracil IV continuously over 46 hours on day 1 for 1 course.



• OxCap: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15 for 1 course.

Patients are then randomized to 1 of 2 treatment arms.

• Neoadjuvant therapy:
  • Arm I: Patients receive 1 of the following chemotherapy regimens:
    • OxMdG: Patients receive oxaliplatin IV over 2 hours and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
    • OxCap: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
  
  
  
  • Arm II: Patients receive 1 of the following regimens:
    • OxMdG + panitumumab: Patients receive panitumumab IV over 60 minutes on day 1 followed by oxaliplatin IV over 2 hours and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
    • OxCap + panitumumab: Patients receive panitumumab IV over 60 minutes on day 1 followed by oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
  
  
  

  Approximately 52 days after beginning chemotherapy, patients in both arms proceed to surgery.




• Surgery: Patients in both arms undergo surgical resection of the primary tumor.



• Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive adjuvant treatment on the same arm for which they received neoadjuvant therapy.
  • Arm I: Patients receive either nine 2-week courses of OxMdG therapy or six 3-week courses of OxCap therapy.
  • Arm II: Patients receive twelve 2-week courses of OxMdG therapy concurrently with panitumumab given every 2 weeks OR eight 3-week courses of OxCap therapy concurrently with panitumumab given every 3 weeks.

Tumor tissue is collected during surgery and blood samples are collected periodically for biomarker studies. Samples are analyzed for the detection of k-ras mutations; the detection of EGFR expression and/or functional genetic polymorphisms of the EGFR gene via PCR; the detection of copy number EGFR gene amplification via fluorescence in situ hybridization (FISH); the detection of EGFR activation via immunohistochemistry (IHC); the detection of EGFR by downstream parameters via western blotting and/or gene expression microarray techniques; for proteomics; and for epigenetics.

Patients complete quality of life questionnaires at baseline, at first course of postoperative chemotherapy, and at 1 year following randomization.

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

Trial Contact Information

Trial Lead Organizations

Birmingham Clinical Trials Unit

Dion Morton, MD, Principal investigator		Ph: 44-121-627-2283

United Kingdom
England
	Birmingham
	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
		Contact Person	Ph:  44-121-472-1311
	Birmingham,
	Birmingham Clinical Trials Unit
		Contact Person	Ph:  44-121-627-2283
			Email: Dion.morton@uhb.nhs.uk
	Gateshead
	Queen Elizabeth Hospital
		Contact Person	Ph:  44-191-482-0000
	Huddersfield, West Yorks
	Huddersfield Royal Infirmary
		Contact Person	Ph:  44-1484-342-000
	Lancaster
	Royal Lancaster Infirmary
		Contact Person	Ph:  44-1524-659-44
	Leeds
	Leeds Cancer Centre at St. James's University Hospital
		Contact Person	Ph:  44-113-206-6400
	Merseyside
	Clatterbridge Centre for Oncology
		Contact Person	Ph:  44-151-334-1155
	Plymouth
	Derriford Hospital
		Contact Person	Ph:  44-175-277-7111
	Southport
	Southport and Formby District General Hospital
		Contact Person	Ph:  44-1704-547-471
	West Bromwich
	Sandwell General Hospital
		Contact Person	Ph:  44-21-553-1831 ext. 3817

Registry Information
Official Title		FOxTROT - Fluoropyrimidine, Oxaliplatin and Targeted Receptor Pre-Operative Therapy: a Controlled Trial in High-Risk Operable Colon Cancer
Trial Start Date		2008-01-16
Trial Completion Date		2012-01-01 (estimated)
Registered in ClinicalTrials.gov		NCT00647530
Date Submitted to PDQ		2008-03-12
Information Last Verified		2008-11-30