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

NCT00647530 | Unknown Phase 2 DMC

• 7 other identifiers: BCTU-FOXTROT-001CDR0000590089ISCRTN 87163246EUDRACT 2007-001987-55EU-20830MREC-07/S0703/57UKCRN 3771
• Study Type: interventional
• Target: 1,053
• Locations: 1 country
• Sites: 10

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.

Conditions

Colorectal Cancer

Keywords

adenocarcinoma of the colon; stage I colon cancer; stage II colon cancer; stage III colon cancer

Outcome Measures

Primary Outcomes (2)

• Freedom from recurrence or persistent disease (including failure of macroscopic disease clearance at primary surgery) within the first two years following 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 of surgery

Secondary Outcomes (11)

• Death from colon cancer

  2 years

• Overall survival

  2 years

• Freedom from recurrence or persistent disease at 2 years (panitumumab comparison)

  2 years

• Pathological assessment of downstaging (involvement of lymph nodes, serosa, and resection margin) and quality of resection specimen

  at surgery

• Quality of resection specimen and distance to high-tie

  post surgery

Study Arms (3)

Pre&Post Op Chemo

EXPERIMENTAL

12 weeks of OxFP neuoadjuvantly followed by surgery and 18 weeks of OxFP

Drug: capecitabine; Drug: fluorouracil; Drug: oxaliplatin

Pre&Post Op Chemo with P-mab

EXPERIMENTAL

12 weeks of OxFP and panitumumab neuoadjuvantly followed by surgery and 18 weeks of OxFP alone.

Biological: panitumumab; Drug: fluorouracil; Drug: oxaliplatin

Post Op Chemo

ACTIVE COMPARATOR

surgery followed by 24 weeks of OxFP.

Drug: capecitabine; Drug: fluorouracil; Drug: oxaliplatin

Interventions

panitumumab BIOLOGICAL

Pre&Post Op Chemo with P-mab

capecitabine DRUG

Post Op Chemo; Pre&Post Op Chemo

fluorouracil DRUG

Post Op Chemo; Pre&Post Op Chemo; Pre&Post Op Chemo with P-mab

oxaliplatin DRUG

Post Op Chemo; Pre&Post Op Chemo; Pre&Post Op Chemo with P-mab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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

You may not qualify if:

• 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%
• 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)

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (10)

Birmingham Clinical Trials Unit

Birmingham, England, B15 2RR, United Kingdom

Location

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust

Birmingham, England, B15 2TH, United Kingdom

Location

Queen Elizabeth Hospital

Gateshead, England, NE9 6SX, United Kingdom

Location

Huddersfield Royal Infirmary

Huddersfield, West Yorks, England, HD3 3EA, United Kingdom

Location

Royal Lancaster Infirmary

Lancaster, England, LA1 4RP, United Kingdom

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Clatterbridge Centre for Oncology

Metropolitan Borough of Wirral, England, CH63 4JY, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL6 8DH, United Kingdom

Location

Southport and Formby District General Hospital

Southport, England, PR8 6PN, United Kingdom

Location

Sandwell General Hospital

West Bromwich, England, B71 4HJ, United Kingdom

Location

Related Publications (3)

• FOxTROT Collaborating Group. Risk of Bowel Obstruction in Patients Undergoing Neoadjuvant Chemotherapy for High-risk Colon Cancer: A Nested Case-control-matched Analysis of an International, Multicenter, Randomized Controlled Trial (FOxTROT). Ann Surg. 2024 Aug 1;280(2):283-293. doi: 10.1097/SLA.0000000000006145. Epub 2023 Nov 10.

  PMID: 37947140 DERIVED

• Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, Palmer A, Seligmann J, Laurberg S, Murakami K, West N, Quirke P, Gray R; FOxTROT Collaborative Group. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023 Mar 10;41(8):1541-1552. doi: 10.1200/JCO.22.00046. Epub 2023 Jan 19.

  PMID: 36657089 DERIVED

• van den Berg I, Smid M, Coebergh van den Braak RRJ, van de Wiel MA, van Deurzen CHM, de Weerd V, Martens JWM, IJzermans JNM, Wilting SM. A panel of DNA methylation markers for the classification of consensus molecular subtypes 2 and 3 in patients with colorectal cancer. Mol Oncol. 2021 Dec;15(12):3348-3362. doi: 10.1002/1878-0261.13098. Epub 2021 Sep 30.

  PMID: 34510716 DERIVED

Related Links

• Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol. 2012 Nov;13(11):1152-60. doi: 10.1016/S1470-2045(12)70348-0. Epub 2012 Sep 25.
• FOxTROT website

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Interventions

Panitumumab; Capecitabine; Fluorouracil; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Dion Morton, MD

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pre- plus Post-operative chemotherapy (+/- Panitumumab) vs standard post-operative chemotherapy.

Study Record Dates

• First Submitted: March 28, 2008
• First Posted: March 31, 2008
• Study Start: May 15, 2008
• Primary Completion: December 23, 2016
• Study Completion: December 31, 2019
• Last Updated: May 17, 2019

Record last verified: 2019-05

Locations

GB (10)