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Phase III Randomized Pilot Study of Neoadjuvant and Adjuvant Fluorouracil and Oxaliplatin With or Without Panitumumab in Patients With Resectable High-Risk Colon Cancer
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
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Protocol IDs
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Phase III
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Biomarker/Laboratory analysis, Treatment
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Active
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Any age
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Other
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BCTU-FOXTROT-001 BCTU-FOxTROT-001, ISCRTN 87163246, EUDRACT 2007-001987-55, EU-20830, MREC-07/S0703/57, UKCRN 3771, NCT00647530
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Objectives Primary - 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 adding panitumumab in the neoadjuvant treatment produces a
measurable increase in antitumor efficacy as measured by tumor 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.
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 1050Outcomes Primary Outcome(s)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
Secondary Outcome(s)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. 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 | | | | Trial Sites
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United Kingdom |
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England |
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Birmingham |
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| | | | Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust |
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Birmingham, |
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| | Birmingham Clinical Trials Unit |
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| Email:
Dion.morton@uhb.nhs.uk |
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Gateshead |
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| | Queen Elizabeth Hospital |
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Huddersfield, West Yorks |
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| | Huddersfield Royal Infirmary |
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Lancaster |
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| | Royal Lancaster Infirmary |
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Leeds |
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| | Leeds Cancer Centre at St. James's University Hospital |
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Merseyside |
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| | Clatterbridge Centre for Oncology |
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Plymouth |
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| | Derriford Hospital |
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Southport |
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| | Southport and Formby District General Hospital |
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West Bromwich |
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| | Sandwell General Hospital |
| | Contact Person | Ph: | 44-21-553-1831 ext. 3817 | | |
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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 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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