Investigating the optimal scheduling of chemotherapy in patients with colorectal and liver cancer

1. Feasibility of the trial to proceed to phase III depends on the following endpoints:
1.1. Mean monthly recruitment in the last 6 months
1.2. Proportion of patients delivered some post-operative chemotherapy
1.3. Proportion of patients who receive all the post-operative chemotherapy required by the protocol
1.4. The surgical complication rate: the proportion of patients experiencing at least one surgical complication within 30 days of surgery (the list of complications which are included are defined below). Each surgical complication will also be rated for severity using a standard scoring system by Clavien (see Appendix XII).
2. A phase III trial will be deemed feasible if the following four criteria are met:
2.1. The mean monthly recruitment rate in the last 6 months of the study is around 4 patients per month across all sites.
2.2. 70% of patients on Arm A and on Arm B are delivered at least some post operative chemotherapy
2.3. Of those who receive some post-operative chemotherapy, 70% receive all the chemotherapy required by the protocol (complete the post-operative chemotherapy protocol)
2.4. The surgical complication rate in each arm is in keeping with expectations such that a difference is likely to be shown in the phase III study (the difference in surgical complication rates between Arm A and Arm B should be within 5% of that mentioned in the proposed phase III sample size calculation in section 8.1, 16% versus 33%, a difference of smaller than this would not be considered clinically meaningful).
3. If the trial proceeds to Phase III the primary outcomes will be as follows:
3.1.For the UK phase III study: surgical complications rate
3.2. For international collaboration: Progression free survival (PFS). PFS will be determined by imaging review. Progression-free survival (PFS) is defined as the time from randomisation to first recurrence/disease progression or death, whichever occurs first. Patients not experiencing recurrence/progression/death will be censored at the date of the last follow-up examination. PFS will be assessed as follows:
In patients with resected metastases (R0 or R1 or R2), PFS will be considered to be the time from randomisation to the first of the following events:
3.2.1. Recurrence/disease progression after surgery
3.2.2. Death
In patients with unresected metastases, PFS will be considered as the time from randomisation to the first of the following events:
3.2.3. Disease progression (whenever it occurs, before or after the planned surgery date)
3.2.4. Death

1. The proportion of chemotherapy received.
2. Peri-operative surgical mortality (within 30 days of surgery).
3. Treatment related toxicity.
4. The effects of treatment on quality of life (QoL) - QoL data will be collected using EORTC QLQ-C30 (version 3), EORTC QLQ - LMC21, EuroQol Questionnaire (EQ-5D)
5. Overall survival (OS) for each treatment arm - OS will be determined by flagging and clinical review. Overall survival is defined as the time interval between the date of randomisation and the date of death. Patients who are still alive when last traced will be censored at the date of last follow-up.
6. Length of stay.
7. Progression-free survival.