Health Condition 1: C182- Malignant neoplasm of ascending colon Health Condition 2: C186- Malignant neoplasm of descending colon Health Condition 3: C183- Malignant neoplasm of hepatic flexure Health Condition 4: C19- Malignant neoplasm of rectosigmoidjunction Health Condition 5: C20- Malignant neoplasm of rectum Health Condition 6: C187- Malignant neoplasm of sigmoid colon Health Condition 7: C185- Malignant neoplasm of splenic flexure Health Condition 8: C184- Malignant neoplasm of transverse
Conditions
Interventions
Intervention1: 1. Oxaliplatin
2. Calcium folinate
3. 5-fluorouracil
: Neoadjuvant Chemotherapy followed by surgery and if needed adjuvant chemotherapy.
Regimen to be decided by local oncology team
IV bolus dexamethasone 8 mg flush line with 5% dextrose (oral dosing also commonly used)
0:00 – 2:00 Calcium Folinate 175mg (or d,l-folinic acid 350 mg) not adjusted for surface area. IV infusion over
IV bolus dexamethasone 8 mg flush line with 5% dextrose
0.00 – 2:00 oxaliplatin 130 mg/m2 IV infusion, 2 hrs, 250 ml 5% dextrose 2:00 flush line with 5% dextrose Evening: capecitabine 1000 mg/m2 p.o.
Sponsors
Christian Medical College Hospital Ludhiana
University of Birmingham
Eligibility
Inclusion criteria
Inclusion criteria: 1.Biopsy-confirmed adenocarcinoma of the colon (or upper rectum if toohigh for radiotherapy) 2.Radiological stage T3-4, N0-2, M0 3.Patient being treated with curative intent 4.Age =18 at the time of registration 5.Tumour tissue is available for MMR/MSI testing (local or central) 6.No clinical or radiological evidence of bowel obstruction 7.Patient able and willing to provide written informed consent for the study 8. Patients unlikely to complete adjuvant chemotherapy due to oncologist assessed frailty, old age or comorbidity 9. Oncologist/CRC specialist-assessed fit to receive 6 weeks of NAC with OxFp (either full or modified dose) and surgery 10. pMMR/MSS tumour status (for Right sided colon tumours) 11. Adequate full blood count: WBC >3.0 x109/l; Plts >100 x109/l; neutrophils =1.5 x109/l. 12. Adequate renal biochemistry: GFR >50 ml/min as assessed by local standards 13. Adequate hepatobiliary function: bilirubin 14. If female and of childbearing potential, must agree to avoid pregnancy during and for 6 months after last dose of study treatment 15. 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 16. Signed the Informed Consent Document for randomization
Exclusion criteria
Exclusion criteria: 1. Any patient for whom radiotherapy is advised by the MDT 2. Strong evidence of distant metastases or peritoneal nodules (cM1), however patients with lung nodules of uncertain significance ( 3. Peritonitis (secondary to perforated tumour) 4. Colonic obstruction that has not been defunctioned 5. Women who are pregnant or breastfeeding 6. Serious medical comorbidity, as assessed by the clinician (such as uncontrolled angina) that will preclude full study participation 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 8. Known dMMR/ MSI-H tumour status 9. Known hypersensitivity to oxaliplatin or fluoropyrimidine therapy 10. Have a peripheral sensitive neuropathy with functional impairment 11. Known complete DPYD deficiency (homozygosity) 12. Recent or concomitant treatment with brivudine, sorivudine or their chemically related analogues.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Proportion of patients alive and disease- free at a minimum of 3 years after randomisation treated with NAC Or Straight to surgery 2. Feasibility of recruitment to the randomized interventions 3. Feasibility of delivery of neoadjuvant chemotherapy 4. Safety and toxicity (both surgical and chemotherapy-related) 5. Completion of surgery post neoadjuvant chemotherapy 6. Feasibility of delivery of timely MMR testing 7. Feasibility of radiology and pathology assessment as part of the trial pathway.Timepoint: 1. Number of patients recruited at 12 months 2. 3 years clinical follow up post treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Tumour regression grade (TRG) 2. Tumour regression score (TRS) 3. Frequency of dMMR mutations (Not Mandatory) 4. Short term efficacy (and association with longer term outcomes) 5. Down staging 6. Safety and toxicity (both surgical and chemotherapy-related) 7. Cancer-related survival Overall survival 8. Surgical morbidity and mortality 9. Histopathological endpoints a) Tumour cell density b) Maximum tumour size c) Depth of invasion d) Apical node involvement e) Peritoneal involvement f) Nodal involvement g) R1/R2 resection ratesTimepoint: 1. Number of patients recruited at 12 months 2. 3 years clinical follow up post treatment | — |
Countries
India
Contacts
Public ContactDr Parvez David Haque
Tata Medical Centre Kolkata
Outcome results
None listed