FOxTROT - Fluoropyrimidine, Oxaliplatin and Targeted Receptor Pre-Operative Therapy: a Controlled Trial in High-Risk Operable Colon Cancer
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- University of Birmingham
- Enrollment
- 1,053
- Locations
- 10
- Primary Endpoint
- Pathological down-staging as measured by depth of extramural spread among patients allocated to preoperative chemotherapy with or without panitumumab
Study Overview
Brief 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.
Detailed 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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Pre&Post Op Chemo
12 weeks of OxFP neuoadjuvantly followed by surgery and 18 weeks of OxFP
Intervention: capecitabine (Drug)
Pre&Post Op Chemo
12 weeks of OxFP neuoadjuvantly followed by surgery and 18 weeks of OxFP
Intervention: fluorouracil (Drug)
Pre&Post Op Chemo
12 weeks of OxFP neuoadjuvantly followed by surgery and 18 weeks of OxFP
Intervention: oxaliplatin (Drug)
Pre&Post Op Chemo with P-mab
12 weeks of OxFP and panitumumab neuoadjuvantly followed by surgery and 18 weeks of OxFP alone.
Intervention: panitumumab (Biological)
Pre&Post Op Chemo with P-mab
12 weeks of OxFP and panitumumab neuoadjuvantly followed by surgery and 18 weeks of OxFP alone.
Intervention: fluorouracil (Drug)
Pre&Post Op Chemo with P-mab
12 weeks of OxFP and panitumumab neuoadjuvantly followed by surgery and 18 weeks of OxFP alone.
Intervention: oxaliplatin (Drug)
Post Op Chemo
surgery followed by 24 weeks of OxFP.
Intervention: capecitabine (Drug)
Post Op Chemo
surgery followed by 24 weeks of OxFP.
Intervention: fluorouracil (Drug)
Post Op Chemo
surgery followed by 24 weeks of OxFP.
Intervention: oxaliplatin (Drug)
Outcomes
Primary Outcomes
Pathological down-staging as measured by depth of extramural spread among patients allocated to preoperative chemotherapy with or without panitumumab
Time Frame: Time of surgery
Freedom from recurrence or persistent disease (including failure of macroscopic disease clearance at primary surgery) within the first two years following randomization
Time Frame: 2 year post randomization
Secondary Outcomes
- Radiological assessment of response to neoadjuvant treatment(prior to surgery)
- Adverse events(throughout the trial, up to 2 years)
- Quality of resection specimen and distance to high-tie(post surgery)
- Overall survival(2 years)
- Pathological assessment of downstaging (involvement of lymph nodes, serosa, and resection margin) and quality of resection specimen(at surgery)
- Lenght of hospital stay(post surgery)
- Surgical morbidity/mortality(30 days post surgery)
- Death from colon cancer(2 years)
- Quality of life by EORTC QLQ C-30 and EuroQol EQ-5D(before surgery, before 1st post-op chemo, 1 year post randomization)
- Chemotherapy toxicity(during chemotherapy administration)
- Freedom from recurrence or persistent disease at 2 years (panitumumab comparison)(2 years)