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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Mrs
Claire
Dimbleby
-
FOxTROT@leeds.ac.uk
More information about this study, what is involved and how to take part can be found on the study website.
Locally advanced but operable colon cancer
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
After lung cancer, bowel (colorectal) cancer is the next most common cause of cancer death in the UK. Doctors usually treat bowel cancer with surgery often followed by chemotherapy to help stop the cancer from coming back. Despite all of the medical advances in recent years, until recently there have been no significant improvements to this treatment approach. However, an international research trial (FOxTROT 1) carried out in the UK, Denmark and Sweden, showed that having some chemotherapy (using the normal chemotherapy drugs for bowel cancer) before surgery (known as neoadjuvant chemotherapy), was safe and reduced the chances of the cancer coming back. However, patients in this study were mainly young and fit. Thanks to funding from Yorkshire Cancer Research, this important study will now be extended to see whether the same procedure is effective with gentler neoadjuvant chemotherapy before surgery in older patients or those with other medical problems (FOxTROT 2). This will be compared to the standard treatment of surgery first. FOxTROT 3 is a trial for younger, fitter patients. FOxTROT 4 (supported by Merck and Pierre Fabre) is a trial for people with a genetic mutation called BRAF. FOxTROT 5 (supported by GSK) is a trial for older patients or those with other medical problems whose tumour has an abnormality called deficient mismatch repair (dMMR).
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
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 confirmed).
2. Suitable for surgical resection and peri-operative SACT
3. No metastatic disease on routine staging investigations.
4. No prior treatment for bowel cancer
5. BRAFV600E mutation present in tumour biopsy (tested locally or centrally)
6. 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 SACT. If Hb remains low despite transfusions, surgery and SACT can be given at the decision of the surgical and oncology teams.
7. Adequate renal biochemistry: GFR >50 ml/min as assessed by local standards
8. Adequate hepatobiliary function: bilirubin < 1.5 x ULN (Patients with Gilbert’s syndrome who have raised bilirubin, but otherwise normal liver function tests are eligible for the study.) AST /ALT <2.5 x ULN.
9. If female and of childbearing potential, must agree to avoid pregnancy during and for 6 months after the 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 6 months after the last dose of study treatment*
11. Signed the Informed Consent Document for randomisation
FOxTROT 5 inclusion criteria:
1. Patients aged 70 years or more and/or with investigator-assessed frailty
2. dMMR and/or MSI-H tumour status by local or central assessment
3. Colon cancer specialist assessed fit to receive neoadjuvant dostarlimab and undergo surgery (refer to section 8.1 and Table 1 for guidance on assessing patient suitability for inclusion in FOxTROT 5)
4. Adequate full blood count: WBC >3.0 x109/l; Platelets >100 x109/l; neutrophils ≥1.5x109/l. Anaemia (Hb <9.0 g/dl) is not an exclusion but should be corrected by transfusion prior to commencement of study treatment. If Hb remains low despite transfusions, surgery and immunotherapy can be given at the discretion of the surgical and oncology teams
5. Adequate renal biochemistry: GFR ≥30 ml/min/1.73m2 for participants with serum creatinine (Cr) ≥1.5 x ULN OR Cr <1.5 x ULN
6. Adequate hepatobiliary function: Bilirubin ≤1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) AST/ALT ≤2.5 x ULN
7. For participants not taking warfarin: INR <1.5 or PT <1.5 x ULN and either PTT or aPTT <1.5 x ULN. Participants taking warfarin may be included on a stable dose with a therapeutic INR <3.5
8. If female and of childbearing potential, must agree to avoid pregnancy during and for 4 months after last dose of study treatment*
9. If male with a partner of childbearing potential, must agree to use adequate, medically app
You may not be able to take part if:
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 therapy2. Have a peripheral sensitive neuropathy with functional impairment3. 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 obstruction2. Known hypersensitivity to oxaliplatin, or fluoropyrimidine therapy3. Prior treatment with any RAF or EGFR inhibitors4. Have a peripheral sensitive neuropathy with functional impairment5. 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 status2. 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 cancers3. 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 allowed4. 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 treatment5. 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 syndrome, toxic epidermal necrolysis, or DRESS syndrome), any grade myocarditis. Non-clinically significant laboratory abnormalities are not exclusionary6. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrolment7. Has any history of interstitial lung disease or pneumonitis8. Cirrhosis or unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal/gastric varices, or persistent jaundice9. Has a history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the study results, interfere with their participation for the full duration of the study intervention, or indicate it is not in the best interests of the participant to participate, in the opinion of the investigator10. Has a history of allogenic stem cell transplantation or organ transplantation11. Has a history of congenital long QT syndrome12. Has a history or evidence of cardiac abnormalities such as serious, uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities within the 6 months prior to enrolment13. Is receiving any other anticancer or experimental therapy14. Received a live vaccine within 30 days of planned start of study therapy15. Has documented presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to enrolment16. Has a positive hepatitis C virus (HCV) antibody test result at screening or within 3 months prior to enrolment. Note: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled, only if a confirmatory HCV RNA test is obtained17. Has a positive HCV RNA test result at screening or within 3 months prior to enrolment. Note: The HCV RNA test is optional and participants with negative HCV antibody test are not required to undergo HCV RNA testing as well18. Is considered, in the investigator’s opinion, a poor medical risk due to severe, uncontrolled medical disorder, non-malignant systemic disease, or active infection requiring systemic therapy.19. Has known history of human immunodeficiency virus (HIV) infection (unless the specific criteria in the FOxTROT 5 protocol are met)20. A known history of severe allergic and/or anaphylactic reactions to chimeric, human or humanized antibodies, fusion proteins, or to dostarlimab or its excipients
______
Previous exclusion criteria as of 17/10/2023 to 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 therapy2. Have a peripheral sensitive neuropathy with functional impairment3. 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 obstruction2. Known hypersensitivity to oxaliplatin, or fluoropyrimidine therapy3. Prior treatment with any RAF or EGFR inhibitors4. Have a peripheral sensitive neuropathy with functional impairment5. 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.
_____
Previous exclusion criteria:
FOxTROT randomisation exclusion criteria:1. Any patient for whom radiotherapy is advised by the multidisciplinary team (MDT)2. Strong evidence of distant metastases or peritoneal nodules (cM1), however patients with lung lesions of uncertain significance (<5 mm) are eligible3. Peritonitis (secondary to perforated tumour)4. Colonic obstruction that has not been defunctioned** 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 exclusion criteria:5. Serious medical comorbidity, as assessed by the leading clinician (such as uncontrolled angina)6. 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%7. Known deficient mismatch repair (dMMR)/microsatellite Instability High (MSI-H) tumour status
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Mrs
Claire
Dimbleby
-
FOxTROT@leeds.ac.uk
More information about this study, what is involved and how to take part can be found on the study website.
The study is sponsored by University of Leeds and funded by Yorkshire Cancer Research; Merck; Pierre Fabre; GSK.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 49772
You can print or share the study information with your GP/healthcare provider or contact the research team directly.
