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

Colorectal Cancer Clinical Trial

Official title: FOxTROT - Fluoropyrimidine, Oxaliplatin and Targeted Receptor Pre-Operative Therapy: a Controlled Trial in High-Risk Operable Colon Cancer

Status Active, not recruiting

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil and oxaliplatin, 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 panitumumab, 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 chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether chemotherapy is more effective with or without panitumumab in treating patients with colon cancer.

PURPOSE: This randomized phase III trial assessing whether preoperative chemotherapy and/or an anti-EGFR monoclonal antibody improve outcome in high risk operable colon cancer.

Clinical Trial Description

FOxTROT is a multi-centre randomised controlled trial (RCT) with the following objectives:

Primary objectives:

• 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.

• To determine if, in patients with RAS-wt tumours, adding panitumumab to neoadjuvant therapy increases anti-tumour activity as measured by tumour shrinkage.

Secondary

• To assess the accuracy of pre-treatment CT scan staging.

• To assess the tolerability of the neoadjuvant therapies.

• To assess the nature and frequency of surgical complications.

• To measure the impact of the treatments on quality of life and on resource usage.

• To assess whether adding panitumumab to neoadjuvant CT reduces 2-year recurrence

• To assess the prognostic and predictive value of tumour biomarkers

• To assess the influence of resectional quality on outcome

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). Planned chemo duration 12 or 24 weeks.

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 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 the following regimen:

• 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.

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

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

• Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive adjuvant treatment on the same arm for which they received neoadjuvant therapy.

• Patients receive either nine 2-week courses of OxMdG therapy or six 3-week courses of OxCap therapy.

Tumour tissue is collected during surgery and blood samples are collected periodically for biomarker studies. Samples are analyzed for the detection of KRAS and NRAS 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 prior to surgery, before 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. ;

Related Conditions & MeSH terms

• Colonic Neoplasms
• Colorectal Cancer
• Colorectal Neoplasms

• NCT number: NCT00647530
• Study type: Interventional
• Source: University of Birmingham
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: May 15, 2008
• Completion date: December 31, 2019