Clinical trial NCT03562234: The CLiFF Study: Change in Liver Function and Fat in Pre-operative Chemotherapy for Colorectal Liver Metastases
Official title: The CLiFF Study: A Prospective Evaluation of Change in Liver Function and Fat in Patients With Colorectal Liver Metastases Undergoing Pre-operative Chemotherapy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colorectal Cancer
Liver Metastasis Colon Cancer
Chemotherapy Effect
Obesity
Keywords: Colorectal Cancer
Colorectal Liver Metastases
Obesity Related Cancer
Chemotherapy
Lead sponsor: University of Manchester
Sponsor class: OTHER
Collaborators: name: The Christie NHS Foundation Trust
name: Manchester University NHS Foundation Trust
name: National Institute for Health Research, United Kingdom
name: National Health Service, United Kingdom
name: Humedics GmbH
First posted: 2018-06-19
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with documented resectable or potentially resectable colorectal cancer liver metastases planned to undergo pre-operative standard care chemotherapy at the Christie NHS Foundation Trust,

Brief summary: The CLiFF Study will assess changes in liver function and liver fat in patients with colorectal liver metastases (CLM) undergoing pre-operative chemotherapy before liver resection. There will be no change to the standard treatment for CLM. The change in liver fat will be assessed using novel magnetic resonance techniques and the change in liver function will be measured using a newly-developed fully-licensed breath test to give the most accurate measure of liver function possible.

Understanding if these changes are related or reversible will help to understand the relationship between obesity and cancer. This is an important issue, as obesity is now the second most common cause of cancer worldwide.

Detailed description: Obesity is the second most common cause of cancer in the United Kingdom (UK) and bowel cancer is the third most common cancer. Obesity can increase both the chance of developing bowel cancer and it's progression. Increased liver fat is likely to be important in this process, but it is not easy to measure liver fat accurately without invasive biopsies.

Chemotherapy is often used to treat colorectal liver metastases before surgery. It is known that chemotherapy can increase liver fat and can reduce liver function, however it is not known if these changes are either reversible or related.

Understanding the relationship of these changes and their potential reversibility could help plan the best treatment for colorectal liver metastases and to understand the wider relationship between obesity and cancer.

A Manchester cancer research team have developed new MR (magnetic resonance) scan techniques which are better able to measure liver fat levels without needing invasive biopsies. The researchers also have a newly-developed fully-licensed machine which can measure liver function more accurately by using a breath test (LiMAx test), donated to the team for this study by the manufacturer, Humedics GmbH.

Patients undergoing pre-operative chemotherapy for CLM at the Christie Hospital will be invited to join this study. Their liver fat content will be measured using the new MR techniques and their liver function measured using the LiMAx test. These will be measured before chemotherapy, during chemotherapy, and after they finish. Their normal treatment will remain unchanged. When they undergo liver surgery, the section of removed liver will be analysed for fatty changes to help confirm that the MR scans are accurate.

Eligibility criteria: Inclusion Criteria:

1. Histologically verified adenocarcinoma of the colon or rectum with radiological evidence of potentially resectable liver metastases, with no evidence of unresectable non-hepatic metastatic disease.
2. Pre-operative chemotherapy planned using Oxaliplatin-based chemotherapy regimen (including FOLFOX, XELOX and OXCAP regimens
3. Age greater than or equal to 18 years
4. WHO (World Health Organisation) performance status 0, 1 or 2
5. Adequate haematological and hepatic function defined by: Hb ³ 10g/dl, WBC ³ 3.0 x 109/L, ANC ³ 1.5 x 109/L, platelet count ³ 100,000/ mm3, total bilirubin \< 30 mmol/L, serum AST, ALT and alkaline phosphatase 5 x upper limit of normal
6. Renal function with creatinine clearance 60 mls/min (for full dose) or 30 ml/min for 50%-dose oxaliplatin
7. Patients must have given written informed consent
8. Any woman of childbearing potential must have a negative pregnancy test prior to enrolment in to the study and must take adequate precautions to prevent pregnancy during treatment

Exclusion Criteria:

1. Presence of a medical or psychiatric condition that impairs their ability to give informed consent
2. Presence of any other serious uncontrolled medical conditions
3. Evidence of unresectable non-hepatic metastatic disease
4. Pregnant or lactating women. Adequate contraception must be used in fertile patients
5. Contra-indications to MR scanning

Primary outcomes:
measure: Change in liver fat (hepatic fat fraction)
timeFrame: 21 weeks
measure: Change in liver function
timeFrame: 21 weeks
Secondary outcomes:
measure: Change in liver enzymes
timeFrame: 28 weeks
measure: Change in body mass index (BMI)
timeFrame: 21 weeks
measure: Change in CT-derived anthropometric measurements 1 - Visceral Adipose Tissue (VAT)
timeFrame: 21 weeks
measure: Change in CT-derived anthropometric measurements 2 - Subcutaneous Adipose Tissue (SAT)
timeFrame: 21 weeks
measure: Change in CT-derived anthropometric measurements 3 - Muscle Mass
timeFrame: 21 weeks
measure: Digital histological quantification of hepatic fat
timeFrame: 28 weeks
measure: NAS-CRN grade of steatosis (Non-Alcoholic Steatohepatitis Activity Score Clinical Research Network)
timeFrame: 28 weeks
measure: Post-operative 30 day mortality
timeFrame: 28 weeks
measure: Post-operative 30 day complications using Clavien-Dindo classification
timeFrame: 28 weeks
measure: Post-operative 30 day complications using the Comprehensive Complication Index (CCI)
timeFrame: 28 weeks
measure: Post-operative 30 day complications using the International Study Group for Liver Surgery (ISGLS) complications score
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
Study officials:
affiliation: The Christie NHS Foundation Trust, The University of Manchester
name: Prof A G Renehan, PhD FRCS
role: STUDY_DIRECTOR
References:
citation: Parmar KL, O'Reilly D, Valle JW, Braun M, Naish JH, Williams SR, Lloyd WK, Malcomson L, Cresswell K, Bamford C, Renehan AG. Prospective study of change in liver function and fat in patients with colorectal liver metastases undergoing preoperative chemotherapy: protocol for the CLiFF Study. BMJ Open. 2020 Sep 23;10(9):e027630. doi: 10.1136/bmjopen-2018-027630.