A trial assessing preoperative chemotherapy in patients with locally advanced but operable colon cancer
- Conditions
- ocally advanced but operable colon cancerCancerMalignant neoplasm of colon
- Registration Number
- ISRCTN83842641
- Lead Sponsor
- niversity of Leeds
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 1703
Current inclusion criteria as of 14/08/2024:
FOxTROT Registration Inclusion Criteria:
1. Biopsy-confirmed adenocarcinoma of the colon (or upper rectum if too high for radiotherapy); high-grade dysplasia is acceptable with unequivocal radiological evidence of invasive cancer*
2. Radiological stage T3-4, N0-2, M0
3. Patient being treated with curative intent
4. Tumour tissue is available for molecular testing (local or central)
5. Age =18 years at the time of registration
6. Patient able and willing to provide written informed consent for the study
* Patients with synchronous colonic tumours are eligible if the most advanced tumour meets the criteria above (please note MMR/MSI testing requirements for randomisation depending upon the location of the most advanced tumour)
FOxTROT 2 Inclusion Criteria:
1. Patients will be unsuitable for mFOLFOXIRI due to oncologist assessed frailty or comorbidity
2. Proficient mismatch repair (pMMR)/MSS tumour status for right sided tumours
3. Colorectal cancer (CRC) specialist-assessed fit to receive 6 weeks of NAC with OxFp (either full or modified dose) and surgery
4. Adequate full blood count: white blood cell (WBC) >3.0 x 10e9/l; platelets (PLTs) >100 x 10^9/l.
5. Anaemia (Hb <10.0 g/dl) is not an exclusion, but should be corrected by transfusion prior to
6. surgery and chemotherapy. If Hb remains low despite transfusions, surgery and chemotherapy can be given at the decision of the surgical and oncology teams.
7. Adequate renal biochemistry: glomerular filtration rate (GFR) >50 ml/min as assessed by local standards
8. Adequate hepatobiliary function: bilirubin <1.5 upper limit of normal (ULN) (patients with Gilbert’s syndrome who have raised bilirubin but otherwise normal liver function tests are eligible for the study)
9. If female and of childbearing potential must agree to avoid pregnancy during and for 6 months after last dose of 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. Signed the Informed Consent Document for randomisation
FOxTROT 3 Inclusion Criteria:
1. Patients need to be fit and suitable for mFOLFOXIRI. There is no fixed age cut-off, but most patients will be under 70 years.
2. pMMR/MSS tumour status for right sided tumours
3. Adequate full blood count: WBC >3.0 x10^9/l; Neutrophils =1.5 x10^9/l; Plts >100 x10^9/l. Anaemia (Hb < 100 g/l) 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.
4. Adequate renal biochemistry: glomerular filtration rate (GFR) >50 ml/min as assessed by local standards
5. Adequate hepatobiliary function: bilirubin <1.5 upper limit of normal (ULN) (patients with Gilbert’s syndrome who have raised bilirubin but otherwise normal liver function tests are eligible for the study)
6. If female and of childbearing potential must agree to avoid pregnancy during and for 6 months after last dose of study treatment
7. 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
8. Signed the Informed Consent Document for randomisation
FOxTROT 4 inclusion criteria:
1. pMMR/MSS colon adenocarcinoma (histologically confir
Current exclusion criteria as of 14/08/2024:
FOxTROT registration exclusion criteria:
1. Any patient for whom radiotherapy is advised by the multidisciplinary team (MDT)
2. Cases with a high index of suspicion of distant metastases or peritoneal nodules (cM1). However, cases with indeterminate abnormalities should be managed and investigated as per standard local MDT procedures and can be considered for trial entry if the MDT opinion is that these are considered most likely to be benign.
3. Colonic obstruction that has not been defunctioned*
4. Women who are pregnant or breastfeeding
* Obstructed patients cannot be included in the FOxTROT trials, unless the obstruction has been relieved. This would usually be by defunctioning. Patients may also be stented, but there is more limited safety data on this and these cases should be individually discussed with the Trial Management Group (TMG).
FOxTROT 2, FOxTROT 3 and FOxTROT 4 Exclusion Criteria:
1. Serious medical comorbidity, as assessed by the leading clinician (such as uncontrolled angina)
2. 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 <10%
3. Known deficient mismatch repair (dMMR)/microsatellite Instability High (MSI-H) tumour status
FOxTROT 3 Additional Exclusion Criteria:
1. Known hypersensitivity to oxaliplatin, irinotecan or fluoropyrimidine therapy
2. Have a peripheral sensitive neuropathy with functional impairment
3. Have a severe chronic inflammatory bowel condition.
4. Known complete DPYD deficiency (homozygosity)
5. Recent or concomitant treatment with brivudine, sorivudine (or their chemically related analogues), St John’s Wort.
FOxTROT 4 Additional Exclusion Criteria:
1. Impending bowel obstruction
2. Known hypersensitivity to oxaliplatin, or fluoropyrimidine therapy
3. Prior treatment with any RAF or EGFR inhibitors
4. Have a peripheral sensitive neuropathy with functional impairment
5. Have a severe chronic inflammatory bowel condition.
6. Known complete DPYD deficiency (homozygosity)
7. Recent or concomitant treatment with brivudine, sorivudine (or their chemically related analogues), St John’s Wort.
FOxTROT 5 Exclusion Criteria:
1. Known pMMR or MSS/MSI-L colonic tumour status
2. Has a known additional malignancy that progressed or required active treatment within the past 2 years. Exceptions include adequately treated superficial skin cancers, superficial bladder cancers, and other in situ cancers
3. Is immunocompromised in the opinion of the investigator, is receiving any immunosuppressive medication, or has received systemic corticosteroids (>10mg prednisolone daily, or equivalent) within 7 days of first dose of study intervention. Use of inhaled steroids, local injection of steroids, topical steroids, and steroidal eye drops are allowed
4. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. levothyroxine) is not considered a form of systemic treatment
5. Experienced any of the following with prior immunotherapy: any Grade 3 or higher immune-related adverse reaction (irAR), anygrade immune-related severe neurologic events (e.g. myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré syndrome, or transverse myelitis), any grade exfoliative dermatitis (Steven-Johnson syndrom
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method