Plain English Summary
Background and study aims
Colorectal cancer is cancer that begins in the large bowel. When a cancer spreads to the liver, the tumours that form are called liver metastases. Operable/resectable liver metastases are metastases that can be removed with surgery. The aim of this study is to compare two treatment strategies for patients who have operable liver metastases from colorectal cancer. We will compare the side effects following surgery and chemotherapy, quality of life and survival for the two strategies. This will tell us whether it is possible to conduct a larger study to determine which strategy is better for patients.
Who can participate?
Patients aged 18 or over with colorectal cancer and operable liver metastases.
What does the study involve?
Patients are randomly allocated to one of two groups. Patients in one group undergo surgery to remove their liver metastases and are then treated for 24 weeks with standard chemotherapy. Patients in the other group undergo chemotherapy treatment for 12 weeks before and 12 weeks after surgery. After completion of the study treatment both groups are followed up every 3 months for 2 years, and every 6 months thereafter for a further 3 years or until their disease progresses.
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
Southampton University Hospitals NHS Trust (UK).
When is the study starting and how long is it expected to run for?
October 2011 to December 2012.
Who is funding the study?
Clinical Trials Awards and Advisory Committee (CTAAC) (UK).
Who is the main contact?
Elizabeth Dixon
Trial website
Additional identifiers
EudraCT number
2011-003052-40
ClinicalTrials.gov number
Protocol/serial number
10838
Study information
Scientific title
An exploratory study to investigate the optimal scheduling of chemotherapy in patients with operable colorectal liver metastases
Acronym
Study hypothesis
To determine whether it is feasible to recruit to a trial of peri-operative versus post operative chemotherapy.
Ethics approval
NRES Committee South Central - Southampton B, 07/09/2011, ref: 11/SC/0293
Study design
Randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Colorectal Cancer; Disease: Liver
Intervention
Arm A: surgery to resect colorectal liver metastases followed by 24 weeks standard chemotherapy. Arm B: 12 weeks of standard care chemotherapy (mFOLFOX, CAPOX or mFOLFIRI) pre-operatively, surgery to resect colorectal liver metastases, then 12 weeks of standard care chemotherapy post-operatively. Followed up after 60 months.
Intervention type
Mixed
Phase
Drug names
Primary outcome measure
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
Secondary outcome measures
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.
Overall trial start date
01/10/2011
Overall trial end date
31/12/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Confirmed colorectal adenocarcinoma
2. Presence of potentially resectable colorectal cancer liver metastases without detectable extra-hepatic tumour that cannot be completely resected
3. 18 years of age or older
4. Fit for chemotherapy and surgery
5. Eastern Cooperative Oncology Group (ECOG) performance status = 2
6. Adequate hematologic, renal and hepatic function
7. No prior chemotherapy for metastatic disease
8. Adjuvant chemotherapy may have been given if >6 months previously
9. If oxaliplatin has been given as adjuvant, irinotecan may be used
10. Rectal chemoradiotherapy must be completed > 1 month before treatment
11. Male or female participants
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 78; UK Sample Size: 78
Participant exclusion criteria
1. Patients in whom there is an indication for chemotherapy to facilitate a R0 resection
2. Patients in whom radio frequency ablation is felt to be an essential component of treatment
3. Positive pregnancy test
Recruitment start date
01/10/2011
Recruitment end date
31/12/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Southampton University Hospitals NHS Trust
Southampton
SO16 6YD
United Kingdom
Sponsor information
Organisation
Southampton University Hospitals NHS Trust (UK)
Sponsor details
Cancer Care Directorate
B Level
Mailpoint WRE
Royal South Hants Hospital
Graham Road
Southampton
SO14 0YG
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Clinical Trials Awards and Advisory Committee (CTAAC) ref: C317/A12358
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list