Colorectal cancer Cancer Malignant neoplasm of rectosigmoid junction
Conditions
Interventions
For patients with colorectal cancer with synchronous hepatic metastases, the study compares the classic approach of bowel cancer surgery first, followed by neoadjuvant chemtoherapy and then liver rese
Sponsors
Central Manchester University Hospitals NHS Foundation Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to be eligible for inclusion, patients must fulfil the following criteria: 1. Over 18 years of age 2. Able to give informed consent 3. Have a histological diagnosis of colorectal cancer 4. No prior history of malignancy 5. Have radiological evidence on either contrast-enhanced computed tomography or contrast-enhanced magnetic resonance scanning of hepatic metastases at the time of diagnosis of the primary tumour or within 3 months thereof. (Liver metastases should not be biopsied) 6. Liver metastatic burden feasible for surgical resection as agreed by an appropriately constituted multi-disciplinary team or to be downstageable for resection by neoadjuvant chemotherapy 7. Computed tomographic and/or 18fluoro-deoxyglucose positron emission tomographic (FDG-PET) of the absence of pulmonary metastases 8. Magnetic resonance scan assessment of rectal primary tumours 9. World Health Organisation performance status (PS) 0, 1 or 2 (see Appendix 2) and considered by both multidisciplinary team and a specialist oncologist to be suitable for chemotherapy. 10. Baseline laboratory tests (within 1 week prior to randomisation): neutrophils ¡Ý 1.5 x109/l and platelet count ¡Ý 100 x109/serum bilirubin ¡Ü 1.25 x upper limit of normal (ULN), alkaline phosphatase ¡Ü 5 x ULN and serum transaminase (either AST or ALT) ¡Ü 2.5 x ULN, estimated creatinine clearance (Cockcroft; appendix VIII) >50ml/min or measured GFR (EDTA clearance) >50 ml/min 11. For women of childbearing potential, negative pregnancy test and adequate contraceptive. Adequate contraception for men. 12. Consent to allow surplus pathological material to be analysed for translational research projects (patients may decline participation in this supplementary component and still participate in the main trial).
Exclusion criteria
Exclusion criteria: 1. Patients who are under 18 years of age 2. Patients who are unable to give informed consent 3. Patients who are unfit for the chemotherapy regimens in this protocol, for example: severe uncontrolled concurrent medical illness (including poorly-controlled angina or very recent myocardial infarction, i.e. in previous 3 months) likely to interfere with protocol treatments 4. Any psychiatric or neurological condition which is felt likely to compromise the patient's ability to give informed consent or to comply with oral medication 5. Partial or complete bowel obstruction not amenable to resolution by stent or diversion 6. Pre-existing neuropathy (> grade 1) 7. Patients requiring on-going treatment with a contraindicated concomitant medication 8. Patients with another previous or current malignant disease 9. Patients with known hypersensitivity reactions to any of the components of the study treatments 10. Patients with brain metastases 11. Female patients who are lactating 12. Patients who have received prior chemotherapy with oxaliplatin 13. Patients with a personal or family history suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency or with known DPD deficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Is there disease-free survival 12 months after enrolment into protocol with the new "reverse" approach to the management of patients with colorectal cancer with synchronous liver metastases compared with classical management | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Disease progression in patients who are not disease-free at the end of protocol: The most sensitive measure of change is likely to involve a metric incorporating tumour size. There is evidence that CT-based volumetric assessment of metastases (seeded region growing method, slice-based segmentation or threshold-based segmentation) is more accurate for assessment of disease progression than the RECIST 1.1 method of largest axial diameter. It is acknowledged that although RECIST criteria provide an objective means of assessment of solid tumour response to treatment, there is a risk of inter-observer bias. Further, RECIST criteria may be insufficient to assess response to treatment in patients with colorectal liver metastases treated by biologic agents such as bevacizumab. Thus, disease progression at end of protocol will be assessed by RECIST 1.1 criteria and compared to volumetric assessment. 2. Timelines for completion of treatment protocol: This is defined as the amount of time in days from enrolment to completion of full protocol. In the reverse protocol, patients may complete the protocol without rectal cancer resection if there is a complete oncological response and a watch and wait policy is adopted. 3. Failure to complete treatment protocol: This is defined as drop-out prior to completion of allocated arm. It will be further categorised as due to disease progression, patient choice or un-related to colorectal cancer (for example myocardial infarction) and will be recorded as the timepoint in days from enrolment. 4. Resection margin status: R0 bowel resection and R0 liver resection (no residual cancer status after colorectal resection and after liver resection). 5. Complication and treatment-related morbidity profiles: Complications will be recorded prospectively according to the criteria defined above (see treatments) and assessed at the end of the study. Complication profiles in patients in the reverse arm will be compared to those in the classic ar | — |
Countries
United Kingdom
Outcome results
None listed