- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00647530
Fluorouracil and Oxaliplatin With or Without Panitumumab In Treating Patients With High-Risk Colon Cancer That Can Be Removed by Surgery (FOxTROT)
FOxTROT - Fluoropyrimidine, Oxaliplatin and Targeted Receptor Pre-Operative Therapy: a Controlled Trial in High-Risk Operable Colon Cancer
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.
Study Overview
Status
Conditions
Intervention / Treatment
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
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
England
-
Birmingham, England, United Kingdom, B15 2TH
- Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
-
Birmingham,, England, United Kingdom, B15 2RR
- Birmingham Clinical Trials Unit
-
Gateshead, England, United Kingdom, NE9 6SX
- Queen Elizabeth Hospital
-
Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
- Huddersfield Royal Infirmary
-
Lancaster, England, United Kingdom, LA1 4RP
- Royal Lancaster Infirmary
-
Leeds, England, United Kingdom, LS9 7TF
- Leeds Cancer Centre at St. James's University Hospital
-
Plymouth, England, United Kingdom, PL6 8DH
- Derriford Hospital
-
Southport, England, United Kingdom, PR8 6PN
- Southport and Formby District General Hospital
-
West Bromwich, England, United Kingdom, B71 4HJ
- Sandwell General Hospital
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Wirral, England, United Kingdom, CH63 4JY
- Clatterbridge Centre for Oncology
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA
- Histologically proven adenocarcinoma of the colon or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer.
A candidate for adjuvant oxaliplatin/ fluoropyrimidine chemotherapy based on:
- Either radiological high risk (rT4 or rT3 tumour with extramural extension ≥ 5mm)
- Or radiological intermediate risk (rT3 tumour with <5mm extramural extension) and younger age/good general health
- Patients presenting with acute colonic obstruction may enter the trial only after obstruction is relieved by a successful defunctioning stoma, and when recovered to a fitness level consistent with the other eligibility criteria
- Adequate full blood count: WBC >3.0 x109/l; Plts >100 x109/l. Anaemia (Hb < 10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams.
- Adequate renal biochemistry: GFR >50 ml/min calculated by the Wright or Cockroft formula or EDTA clearance >70 ml/min
- Adequate hepatobiliary function: bilirubin < 25 μmol/l (Patients with Gilbert's syndrome who have raised bilirubin but otherwise normal liver function tests are eligible for the study.)
- Aged 18 or over
- WHO performance status of 0, 1 or 2
If female and of childbearing potential, must:
- Have a negative pregnancy test ≤72hours prior to initiating study treatment
- Agree to avoid pregnancy during and for 6 months after study treatment
If male with a partner of childbearing potential, must:
- Agree to use adequate, medically approved, contraceptive precautions during and for 90 days after the last dose of study treatment
- Patient able and willing to provide written informed consent for the study
EXCLUSION CRITERIA
- Any patient for whom radiotherapy is advised by the MDT
- Strong evidence of distant metastases or peritoneal nodules (M1)
- Peritonitis (secondary to perforated tumour)
- Colonic obstruction that has not been defunctioned
- Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent (<6 months) MI
- Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery
- Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk <5%
ADDITIONAL EXCLUSION CRITERIA FOR PANITUMUMAB RANDOMISATION
- RAS-mutant or unknown RAS status tumours
- Allocated post-operative chemotherapy
- History of interstitial pneumonitis or pulmonary fibrosis
- History of severe or life-threatening hypersensitivity reactions
- Serum magnesium levels within the normal range at trial entry (which can include intravenous correction)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Pre&Post Op Chemo
12 weeks of OxFP neuoadjuvantly followed by surgery and 18 weeks of OxFP
|
|
EXPERIMENTAL: Pre&Post Op Chemo with P-mab
12 weeks of OxFP and panitumumab neuoadjuvantly followed by surgery and 18 weeks of OxFP alone.
|
|
ACTIVE_COMPARATOR: Post Op Chemo
surgery followed by 24 weeks of OxFP.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
2 year post randomization
|
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
|
Time of surgery
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall survival
Time Frame: 2 years
|
2 years
|
Death from colon cancer
Time Frame: 2 years
|
2 years
|
Freedom from recurrence or persistent disease at 2 years (panitumumab comparison)
Time Frame: 2 years
|
2 years
|
Pathological assessment of downstaging (involvement of lymph nodes, serosa, and resection margin) and quality of resection specimen
Time Frame: at surgery
|
at surgery
|
Quality of resection specimen and distance to high-tie
Time Frame: post surgery
|
post surgery
|
Radiological assessment of response to neoadjuvant treatment
Time Frame: prior to surgery
|
prior to surgery
|
Quality of life by EORTC QLQ C-30 and EuroQol EQ-5D
Time Frame: before surgery, before 1st post-op chemo, 1 year post randomization
|
before surgery, before 1st post-op chemo, 1 year post randomization
|
Lenght of hospital stay
Time Frame: post surgery
|
post surgery
|
Surgical morbidity/mortality
Time Frame: 30 days post surgery
|
30 days post surgery
|
Chemotherapy toxicity
Time Frame: during chemotherapy administration
|
during chemotherapy administration
|
Adverse events
Time Frame: throughout the trial, up to 2 years
|
throughout the trial, up to 2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Dion Morton, MD, University of Birmingham
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Colorectal Neoplasms
- Colonic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Fluorouracil
- Capecitabine
- Oxaliplatin
- Panitumumab
Other Study ID Numbers
- BCTU-FOXTROT-001
- CDR0000590089 (REGISTRY: PDQ (Physician Data Query))
- ISCRTN 87163246
- EUDRACT 2007-001987-55
- EU-20830
- MREC-07/S0703/57
- UKCRN 3771
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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