Condition category
Cancer
Date applied
28/11/2006
Date assigned
30/03/2007
Last edited
26/01/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Laura Magill

ORCID ID

Contact details

Birmingham Clinical Trials Unit (BCTU)
Institute of Applied Health Research
College of Medical and Dental Sciences
Public Health Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

2007-001987-55

ClinicalTrials.gov number

NCT00647530

Protocol/serial number

N/A

Study information

Scientific title

Fluoropyrimidine, Oxaliplatin and Targeted Receptor pre-Operative Therapy: a controlled trial in high-risk operable colon cancer

Acronym

FOxTROT

Study hypothesis

For patients with high risk, operable colon cancer:
1. Does giving potent Oxaliplatin/FluoroPyrimidine (OxFP) chemotherapy preoperatively facilitate surgical clearance and eradicate micrometastases more effectively than delayed post-operative chemotherapy?
2. Does the addition of the Epidermal Growth Factor Receptor (EGFR)-targeted therapy, panitumumab, enhance the efficacy of OxFP?

Ethics approval

West Glasgow Research Ethics Committee, 05/06/2007, ref: 07/S0703/57

Study design

Open multicentre randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

High risk, operable colon cancer

Intervention

Current interventions as of 05/01/2017:

An open, multicentre, randomised controlled trial.
First phase: randomised phase II assessing tolerability, feasibility and radiological/pathological downstaging.
Second phase: randomised phase III trial with primary endpoint relapse-free survival.

Arm A: Six weeks of pre-operative oxaliplatin/fluoropyrimidine chemotherapy followed by surgery then 18 weeks of post-operative oxaliplatin/fluoropyrimidine chemotherapy
Arm B: The same chemotherapy with concomitant panitumumab for the first six weeks
Arm C: Surgery then twenty four weeks of post-operative oxaliplatin/fluoropyrimidine chemotherapy

The two allowable oxaliplatin/fluoropyrimidine chemotherapy regimens are twelve two-week courses of Oxaliplatin and Modified deGramont (OxMdG), or eight three-week courses of Oxaliplatin and Capecitabine (OxCap). Patients randomised to receive panitumumab receive this by intravenous (IV) infusion over 60 minutes at 6 mg/kg on day one of each of the first three two-week OxMdG cycles, immediately prior to the start of the chemotherapy regimen.

Post-operative adjuvant therapy will be given, regardless of trial arm and operative histology.

Previous interventions:

An open, multicentre, randomised controlled trial.
First phase: randomised phase II assessing tolerability, feasibility and radiological/pathological downstaging.
Second phase: randomised phase III trial with primary endpoint relapse-free survival.

Arm A: Six weeks of pre-operative oxaliplatin/fluoropyrimidine chemotherapy followed by surgery then 18 weeks of post-operative oxaliplatin/fluoropyrimidine chemotherapy
Arm B: The same chemotherapy with concomitant panitumumab for the first six weeks
Arm C: Surgery then twenty four weeks of post-operative oxaliplatin/fluoropyrimidine chemotherapy
Arm D: Schedule C with concomitant panitumumab for the first six weeks of post operative therapy

The two allowable oxaliplatin/fluoropyrimidine chemotherapy regimens are twelve two-week courses of Oxaliplatin and Modified deGramont (OxMdG), or eight three-week courses of Oxaliplatin and Capecitabine (OxCap). Patients randomised to receive panitumumab receive this by intravenous (IV) infusion over 60 minutes at 6 mg/kg on day one of each of the first three two-week OxMdG cycles; or at 9 mg/kg on day one of each of the first two three-week OxCap cycles, immediately prior to the start of the chemotherapy regimen.

Post-operative adjuvant therapy will be given, regardless of trial arm and operative histology.

Intervention type

Drug

Phase

Phase II/III

Drug names

Fluoropyrimidine, oxaliplatin, panitumumab

Primary outcome measure

Current primary outcome measures as of 26/01/2018:
1. Freedom from recurrent of persistent disease (including failure of macroscopic disease clearance at primary surgery) within the first two years following randomisation
2. Pathological down-staging as measured by depth of extramural spread among patients allocated to preoperative chemotherapy with or without panitumumab

Previous primary outcome measures:
1. Pre- plus post-operative versus post-operative chemotherapy: freedom from recurrence (or residual disease) at two years after randomisation (arms A and B versus C and D)
2. Panitumumab versus not: pathological down-staging (arm B versus A)

Secondary outcome measures

Current secondary outcome measures as of 26/01/2018:
1. Death from colon cancer
2. Overall survival
3. Freedom from recurrence or persistent disease at 2 years (panitumumab comparison)
4. Pathological assessment of downstaging (involvement of lymph nodes, serosa, and resection margin) and quality of resection specimen
5. Quality of resection specimen and distance to high-tie
6. Radiological assessment of response to neoadjuvant treatment
7. Quality of life by EORTC QLQ C-30 and EuroQol EQ-5D
8. Length of hospital stay
9. Surgical morbidity/mortality
10. Chemotherapy toxicity
11. Adverse events

Previous secondary outcome measures:
1. Death from colon cancer
2. Overall survival
3. Health-related quality of life
4. Pathological assessment of down-staging (involvement of lymph nodes, serosa, resection margin), and quality of resection specimen
5. Radiological assessment of response in neoadjuvant treatment arms
6. CarcinoEmbryonic Antigen (CEA) level following neo-adjuvant therapy
7. Health Service resource usage
8. Adverse events
9. Surgical morbidity/mortality

Overall trial start date

01/01/2007

Overall trial end date

31/12/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 26/01/2018:
1. Histologically proven adenocarcinoma of the colon or high grade dysplasia on histology plus unequivocal radiological evidence of invasive cancer
2. A candidate for adjuvant oxaliplatin/ fluoropyrimidine chemotherapy based on:
2.1. Either radiological high risk (rT4 or rT3 tumour with extramural extension ≥ 5mm)
2.2. Or radiological intermediate risk (rT3 tumour with <5mm extramural extension) and younger age/good general health
3. 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
4. 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.
5. Adequate renal biochemistry: GFR >50 ml/min calculated by the Wright or Cockroft formula or EDTA clearance >70 ml/min
6. 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.)
7. Aged 18 or over
8. WHO performance status of 0, 1 or 2
9. If female and of childbearing potential, must:
9.1. Have a negative pregnancy test ≤72hours prior to initiating study treatment
9.2. Agree to avoid pregnancy during and for 6 months after study treatment
10. 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
11. Patient able and willing to provide written informed consent for the study


Previous inclusion criteria:
1. Histologically proven colon cancer with a radiological staging of T3, NX, M0
2. Computed Tomography (CT) scan criteria of poor prognosis (T4 or T3 and more than 5 mm extramural depth and/or probable nodal involvement and/or probable vascular invasion)
3. Fit for the neoadjuvant treatments
4. Patients who have presented with acute colonic obstruction if a successful defunctioning or stent procedure has been performed
5. Patients able and willing to provide written informed consent for the study

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

150 in the pilot phase then a further 900

Participant exclusion criteria

Current exclusion criteria as of 26/01/2018:
1. MorbidityAny patient for whom radiotherapy is advised by the MDT
2. Strong evidence of distant metastases or peritoneal nodules (M1)
3. Peritonitis (secondary to perforated tumour)
4. Colonic obstruction that has not been defunctioned
5. Serious medical comorbidity, eg uncontrolled inflammatory bowel disease, uncontrolled angina or recent (<6 months) MI
6. Another serious medical condition judged to compromise ability to tolerate neoadjuvant therapy and/or surgery
7. 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
1. RAS-mutant or unknown RAS status tumours
2. Allocated post-operative chemotherapy
3. History of interstitial pneumonitis or pulmonary fibrosis
4. History of severe or life-threatening hypersensitivity reactions
5. Serum magnesium levels within the normal range at trial entry (which can include intravenous correction)

Previous exclusion criteria:
1. Tumour within 15 cm of the anal verge as judged by sigmoidoscopy, or below the level of the sacral promontory, as judged by sagittal CT
2. Indication for radiotherapy
3. Evidence of disseminated disease (M1)
4. Peritonitis (secondary to perforated tumour)
5. Under the age of 18 or pregnant
6. Serious medical co-morbidity

Recruitment start date

01/04/2008

Recruitment end date

23/12/2016

Locations

Countries of recruitment

Denmark, Sweden, United Kingdom

Trial participating centre

University of Birmingham
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Birmingham
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

http://www.bham.ac.uk/default.asp

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/23017669

Publication citations

  1. Results

    Foxtrot Collaborative Group, Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial., Lancet Oncol., 2012, 13, 11, 1152-1160, doi: 10.1016/S1470-2045(12)70348-0.

Additional files

Editorial Notes

26/01/2018: The primary and secondary outcome measures have been updated. The recruitment end date has been updated from 31/12/2016 to 23/12/2016. 05/01/2017: the overall trial end date was changed from 01/03/2018 to 31/12/2019. 19/02/2016: the recruitment end date was changed from 31/12/2015 to 31/12/2016. 10/07/2015: the overall trial end date was changed from 31/12/2015 to 01/03/2018. 25/06/2015: Sweden and Denmark were added to the countries of recruitment.