Colorectal Cancer With Liver-limited Synchronous Metastases: an Inception Cohort Study of Standardised Care Pathways

NCT02456285 | Completed DMC

• 1 other identifier: R03880
• Study Type: observational
• Target: 123
• Locations: 1 country
• Sites: 1

Brief Summary

Background When first diagnosed, colorectal cancer has already metastasized in about 20% of patients to the liver or further (termed synchronous disease). For patients with metastatic disease limited to the liver, major surgery to resect both the primary colorectal cancer and the liver metastasis provides 5-year survival rates of 25-40%. Conventional surgery removes the colorectal primary first, followed by adjuvant chemotherapy, and then resection of the liver metastasis. Surgical advances make synchronous resection (removing both primary and liver metastasis together) and liver-first resection possible. Currently, there is no conclusive evidence to show which approach improves morbidity or survival, and therefore there is no optimum clinical pathway. Treatment is decided at multidisciplinary team (MDT) meetings and is dependent on multiple factors: cancer staging, patient health and preferences, and clinical experience. Methods "Colorectal cancer with Synchronous liver-limited hepatic Metastasis: an Inception Cohort (CoSMIC)", will consent and recruit patients with a new diagnosis of synchronous colorectal cancer limited to the liver. Patients will be recruited at Manchester Royal Infirmary (a National Health Service (NHS) regional cancer-network approved Hepato-pancreato-biliary specialist centers over 2 years using standardized data collection. The sequence of treatment received by each patient, and factors influencing treatment decisions, will be recorded and evaluated against European Society of Medical Oncology guidelines. The effect of surgery on patient quality of life, morbidity, mortality and the long-term outcome will be measured and compared for different treatment sequences adjusted for prognostic factors. Anticipated Outputs and Value of Findings Direct comparison of conventional and new surgical sequences will be explored. Patient engagement, use of standardised recording, identifying common clinical patterns and decision making, and understanding sources of variation are essential steps to develop a definite randomized control trial to resolve the optimal clinical pathway.

Conditions

Colorectal Neoplasms; Liver Neoplasms; Neoplasm Metastasis

Outcome Measures

Primary Outcomes (1)

• Adherence to an evidence-informed common pathway assessed using guidelines suggested by the European Society of Medical Oncology (ESMO)

  The first primary outcome measure of CoSMIC is to assess the adherence to an evidence-informed common pathway, using guidelines suggested by the European Society of Medical Oncology (ESMO). These include early use of neo-adjuvant chemotherapy, surgical resection and adjuvant chemotherapy as the final stage. The treatment options within the common pathway standardise initial staging, accommodating treatment for liver metastases according to liver involvement and location of disease as well as different treatment requirements for patients with rectal primary cancer compared to those with colonic primary tumours.

  2 years

Interventions

Primary/Bowel-first Surgery PROCEDURE

Patients undergoing primary/bowel-first surgery as part of a staged curative procedure. The liver metastases will be resected in a second planned operation.

Liver-first surgery PROCEDURE

Patients undergoing liver-first surgery as part of a staged curative procedure. The colorectal primary will be resected in a second planned operation.

Synchronous resection surgery PROCEDURE

Patients undergoing a synchronous colorectal primary resection and liver resection in a single operation.

No surgery PROCEDURE

Patients who have no surgery.

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

The study population will comprise patients with colorectal cancer with liver-limited hepatic metastases referred to the Hepatobiliary Surgical Unit at Manchester Royal Infirmary - a National Health Service (NHS) regional cancer-network approved hepato-pancreato-biliary (HPB) centre with a formally constituted and National Cancer Network peer-review accredited multidisciplinary team (MDT).

You may qualify if:

• Over 18 years of age
• Able to give informed consent
• Have a histological diagnosis of colorectal cancer
• No prior history of malignancy
• Have radiological evidence on either contrast-enhanced computed tomography or contrast-enhanced magnetic resonance scanning of hepatic metastases at the time of diagnosis of the primary tumour or within 3 months thereof. Liver metastases should not be biopsied.
• Computed tomographic and/or 18fluoro-deoxyglucose positron emission tomographic (FDG-PET) evidence of the absence of extrahepatic metastases.
• Magnetic resonance scan assessment of local stage of rectal primary tumours.
• World Health Organisation performance status (PS) 0, 1 or 2 and considered by multidisciplinary team to be suitable for chemotherapy.
• Consent to allow surplus pathological material to be analysed for translational research projects (patients may decline participation in this supplementary component and still participate in the main trial).

You may not qualify if:

• Patients who are under 18 years of age.
• Patients who are unable to give informed consent.
• Patients who are unfit for the chemotherapy regimens in this protocol.
• Any psychiatric or neurological condition assessed by clinical judgement to compromise the patient's ability to give informed consent or to comply with oral medication.
• Partial or complete bowel obstruction not amenable to resolution by stent or diversion.
• Pre-existing neuropathy (\> grade 1).
• Patients with another previous or current malignant disease.
• Patients with known hypersensitivity reactions to any of the components of the study treatments.
• Patients with distant metastases outwith the liver.
• Patients who have received prior chemotherapy with oxaliplatin.
• Patients with a personal or family history suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency or with known DPD deficiency.

Sponsors & Collaborators

• Manchester University NHS Foundation Trust: lead
• University of Warwick: collaborator

Study Sites (1)

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Related Publications (4)

• Siriwardena AK, Mason JM, Mullamitha S, Hancock HC, Jegatheeswaran S. Management of colorectal cancer presenting with synchronous liver metastases. Nat Rev Clin Oncol. 2014 Aug;11(8):446-59. doi: 10.1038/nrclinonc.2014.90. Epub 2014 Jun 3.

  PMID: 24889770 BACKGROUND

• Jegatheeswaran S, Mason JM, Hancock HC, Siriwardena AK. The liver-first approach to the management of colorectal cancer with synchronous hepatic metastases: a systematic review. JAMA Surg. 2013 Apr;148(4):385-91. doi: 10.1001/jamasurg.2013.1216.

  PMID: 23715907 BACKGROUND

• Chan AKC, Mason JM, Baltatzis M, Siriwardena AK; CoSMIC Collaborators. Management of Colorectal Cancer with Synchronous Liver Metastases: An Inception Cohort Study (CoSMIC). Ann Surg Oncol. 2022 Mar;29(3):1939-1951. doi: 10.1245/s10434-021-11017-7. Epub 2021 Oct 30.

  PMID: 34716838 DERIVED

• Siriwardena AK, Chan AKC, Ignatowicz AM, Mason JM; CoSMIC study collaborators. Colorectal cancer with Synchronous liver-limited Metastases: the protocol of an Inception Cohort study (CoSMIC). BMJ Open. 2017 Jun 9;7(6):e015018. doi: 10.1136/bmjopen-2016-015018.

  PMID: 28601828 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Liver Neoplasms; Neoplasm Metastasis

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; Liver Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ajith K Siriwardena, MD, FRCS

  Hepatobiliary Surgery Unit, Manchester Royal Infirmary, United Kingdom

  PRINCIPAL INVESTIGATOR

• James Mason, DPhil

  Durham Clinical Trials Unit, Wolfson Research Institute, Durham University, United Kingdom

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2015
• First Posted: May 28, 2015
• Study Start: May 20, 2015
• Primary Completion: April 30, 2017
• Study Completion: April 30, 2017
• Last Updated: March 16, 2021

Record last verified: 2021-03

Locations

GB (1)