Condition category
Cancer
Date applied
02/09/2011
Date assigned
02/09/2011
Last edited
29/09/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Contact information

Type

Scientific

Primary contact

Mrs Elizabeth Dixon

ORCID ID

Contact details

Clinical Trials Unit
MailPoint 816
Tremona Road
Southampton
SO16 6YD
United Kingdom

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 measures

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

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

http://www.suht.nhs.uk/

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes