The CLiFF Study: Change in Liver Function and Fat in Pre-operative Chemotherapy for Colorectal Liver Metastases

NCT03562234 | Unknown

• 1 other identifier: MD189
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer; Liver Metastasis Colon Cancer; Chemotherapy Effect; Obesity

Keywords

Colorectal Cancer; Colorectal Liver Metastases; Obesity Related Cancer; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Change in liver fat (hepatic fat fraction)

  Change in liver fat (measured as a percentage using MR imaging - the hepatic fat fraction) comparing the baseline pre-chemotherapy measurement at Week 1 with measurements at cessation of chemotherapy (Week 13) and 8 weeks after cessation of chemotherapy (Week 21). The expectation based on relevant literature is that chemotherapy will lead to potentially reversible higher levels of liver fat. Therefore the liver fat measurement (hepatic fat fraction) should be higher at week 13 than at week 1, and if this change is reversible, the liver fat should decrease during the eight weeks following cessation of chemotherapy, resulting in the measurement at Week 21 being lower than week 13.

  21 weeks

• Change in liver function

  Change in liver function measured by LiMAx test (Liver Maximum Capacity), comparing the baseline pre-chemotherapy measurement at week 1 with a measurement mid-chemotherapy (week 7), a measurement at cessation of chemotherapy (Week 13) and a measurement 8 weeks after cessation of chemotherapy (week 21). The expectation from relevant literature is that chemotherapy should cause a reversible deterioration in liver function, therefore the measurement at Week 7 should be lower than week 1, with the measurement at Week 13 then being lower again than week 7. If this deterioration in liver function is reversible, potentially within 8 weeks of stopping chemotherapy as suggested in the literature, then the measurement at Week 21 should be higher than both week 7 and week 13.

  21 weeks

Secondary Outcomes (11)

• Change in liver enzymes

  28 weeks

• Change in body mass index (BMI)

  21 weeks

• Change in CT-derived anthropometric measurements 1 - Visceral Adipose Tissue (VAT)

  21 weeks

• Change in CT-derived anthropometric measurements 2 - Subcutaneous Adipose Tissue (SAT)

  21 weeks

• Change in CT-derived anthropometric measurements 3 - Muscle Mass

  21 weeks

Study Arms (1)

Pre-op Chemotherapy for CLM: MR & LiMAx

Patients undergoing pre-operative chemotherapy for colorectal liver metastases being treated at the Christie NHS (National Health Service) Foundation Trust. No intervention - participants will continue with standard care. Observation of changes in liver fat and liver function measured by MR (Magnetic Resonance) scan and LiMAx test (Maximum liver capacity).

Diagnostic Test: MR; Diagnostic Test: LiMAx

Interventions

MR DIAGNOSTIC_TEST

Liver fat (measured as a percentage - hepatic fat fraction) will be measured by Magnetic Resonance imaging

Pre-op Chemotherapy for CLM: MR & LiMAx

LiMAx DIAGNOSTIC_TEST

Liver function will be measured using the relatively new CE licenced non-invasive LiMAx (Liver Maximum Capacity) test device, manufactured by Humedics GmbH

Pre-op Chemotherapy for CLM: MR & LiMAx

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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,

You may qualify if:

• 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.
• Pre-operative chemotherapy planned using Oxaliplatin-based chemotherapy regimen (including FOLFOX, XELOX and OXCAP regimens
• Age greater than or equal to 18 years
• WHO (World Health Organisation) performance status 0, 1 or 2
• 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
• Renal function with creatinine clearance 60 mls/min (for full dose) or 30 ml/min for 50%-dose oxaliplatin
• Patients must have given written informed consent
• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Manchester: lead
• The Christie NHS Foundation Trust: collaborator
• Manchester University NHS Foundation Trust: collaborator
• National Institute for Health Research, United Kingdom: collaborator
• National Health Service, United Kingdom: collaborator
• Humedics GmbH: collaborator

Study Sites (1)

The Christie NHS Foundation Trust

Manchester, Greater Manchester, M20 4NX, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 32967864 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Obesity

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Prof A G Renehan, PhD FRCS

  The Christie NHS Foundation Trust, The University of Manchester

  STUDY DIRECTOR

Central Study Contacts

Kat L Parmar, MBChB FRCS

CONTACT

07817296021; Kat.Parmar@manchester.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Fellow in Surgery & Cancer Research

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: June 19, 2018
• Study Start: October 22, 2018
• Primary Completion: February 1, 2020
• Study Completion: April 1, 2020
• Last Updated: November 7, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)