An Observational Study of Avastin (Bevacizumab) in Patients With Metastatic Colorectal Cancer (ACORN)

An Observational Study of Avastin® (Bevacizumab) in Combination With Chemotherapy for Treatment of First-line Metastatic Colorectal Adenocarcinoma

This prospective, multi-center, observational study will assess the safety and efficacy of Avastin (bevacizumab) in daily practice in patients with metastatic colorectal cancer who have received no previous treatment for advanced disease and are receiving Avastin in combination with a standard of care first-line chemotherapy regimen. Data will be collected for 1.5 years or until death.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Capecitabine/Oxaliplatin; Drug: Fluorouracil/Folinic Acid/Oxaliplatin; Drug: Capecitabine; Drug: Fluorouracil/Folinic Acid/Irinotecan; Drug: Fluorouracil +/- Folinic Acid

• Study Type: Observational
• Enrollment (Actual): 719

Contacts and Locations

Study Locations

• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Royal United Hospital Bath; Diabetes and Lipid Research, Wolfson Centre
  • Berkshire, United Kingdom, SL2 4HL
    • Wexham Park Hospital; Oncology
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital; Dept of Oncology
  • Bishop Auckland, United Kingdom, DL14 6AD
    • Bishop Auckland Hospital;Oncology Department
  • Blackpool, United Kingdom, FY3 8NR
    • University Hospital of North Staffordhire
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Royal Infirmary; Dept of Medical Oncology C/O Ward15
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre
  • Bury St Edmunds, United Kingdom, IP33 2QZ
    • West Suffolk Hospital Nhs Trust; Gi Corridor
  • Canterbury, United Kingdom, CT1 3NG
    • Kent & Canterbury Hospital
  • Carlisle, United Kingdom, CA2 7HY
    • Cumberland Infirmary; Oncology Department
  • Chelsmford, United Kingdom, CM1 7ET
    • Broomfield Hospital; Oncology
  • Cleveland, United Kingdom, TS19 8PE
    • University Hospital North Tees
  • Cottingham, United Kingdom, HU16 5JQ
    • Castle Hill Hospital; Academic Oncology
  • Darlington, United Kingdom, DL3 6HX
    • Darlington Memorial Hospital
  • Dudley, United Kingdom, DY1 2HQ
    • Russells Hall Hospital; Dept of Hematology
  • Durham, United Kingdom, DH15TW
    • University Hospital of North Durham; Oncology
  • Harrogate, United Kingdom, HG2 8AY
    • Harrogate Hospital
  • Harrow, United Kingdom, HA1 3UJ
    • Northhwick Park Hospital;Oncology Department
  • Ipswich, United Kingdom, IP4 5PD
    • Ipswich Hospital; Oncology Pharmacy
  • Kidderminster, United Kingdom, DY11 6RJ
    • Kidderminster Hospital; Oncology Dept
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital; Dept of Oncology
  • London, United Kingdom, SE18 4QH
    • Queen Elizabeth Hospital
  • London, United Kingdom, SE1 9RT
    • Guys Hosp./Med. Onc./3rd Fl. T; Clinical Trial Office
  • Macclesfield, United Kingdom, SK10 3BL
    • Macclesfield District General Hospital
  • Maidstone, United Kingdom, ME16 9QQ
    • Maidstone & Tonbridge Wells Hospital; Kent Oncology Center
  • Middlesborough, United Kingdom, TS4 3BW
    • The James Cook University Hospital
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • North Shields, United Kingdom, NE29 8NH
    • North Tyneside General Hospital
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon Cancer Centre
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals City Campus
  • Peterborough, United Kingdom, PE3 9GZ
    • Peterborough City Hospital, Edith Cavell Campus; Oncology Department
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital; Gastroenterology
  • Romford, United Kingdom, RM7 0AG
    • Queen's Hospital
  • Scunthorpe, United Kingdom, DN16 7BH
    • Scunthorpe General Hospital; Dept of Oncology
  • Stafford, United Kingdom, ST16 3SA
    • Stafford Hospital; Oncology Department
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Hospital
  • Swindon, United Kingdom, SN3 6BB
    • Great Western Hospital, Swindon Cancer Research Unit; Osprey Unit Level 3
  • Torquay, United Kingdom, TQ2 7AA
    • Torbay Hospital; Oncology
  • Truro, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospital; Dept of Clinical Oncology
  • Walsall, United Kingdom, WS2 9PS
    • Walsall Manor Hospital
  • Winchester, United Kingdom, SO22 5DG
    • Royal Hampshire County Hospital; Winchester & Andover Breast Unit
  • Wolverhampton, United Kingdom, WV10 0QP
    • The Royal Wolverhampton Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients diagnosed with metastatic colorectal cancer

Description

Inclusion Criteria:

• Metastatic colorectal cancer with no previous systemic treatment for advanced disease
• Receiving Avastin in combination with a first-line standard of care chemotherapy regimen
• Avastin initiated at the same time as first-line chemotherapy regimen

Exclusion Criteria:

• Investigational, non-standard of care first-line chemotherapy regimen for treatment of metastatic colorectal cancer
• Contraindication to Avastin

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bevacizumab and Capecitabine/Oxaliplatin; Participants who receive bevacizumab in combination with capecitabine/oxaliplatin	Drug: Bevacizumab; Bevacizumab was administered as part of standard first-line treatment; Other Names: Avastin®; Drug: Capecitabine/Oxaliplatin; Capecitabine/oxaliplatin were administered along with bevacizumab as part of standard first-line treatment
Bevacizumab and Fluorouracil/Folinic Acid/Oxaliplatin; Participants who receive bevacizumab in combination with fluorouracil/folinic acid/oxaliplatin	Drug: Bevacizumab; Bevacizumab was administered as part of standard first-line treatment; Other Names: Avastin®; Drug: Fluorouracil/Folinic Acid/Oxaliplatin; Fluorouracil/folinic acid/oxaliplatin were administered along with bevacizumab as part of standard first-line treatment
Bevacizumab and Capecitabine; Participants who receive bevacizumab in combination with capecitabine	Drug: Bevacizumab; Bevacizumab was administered as part of standard first-line treatment; Other Names: Avastin®; Drug: Capecitabine; Capecitabine was administered along with bevacizumab as part of standard first-line treatment
Bevacizumab and Fluorouracil/Folinic Acid/Irinotecan; Participants who receive bevacizumab in combination with fluorouracil/folinic acid/irinotecan	Drug: Bevacizumab; Bevacizumab was administered as part of standard first-line treatment; Other Names: Avastin®; Drug: Fluorouracil/Folinic Acid/Irinotecan; Fluorouracil/folinic acid/irinotecan were administered along with bevacizumab as part of standard first-line treatment
Bevacizumab and Capecitabine/Irinotecan; Participants who receive bevacizumab in combination with capecitabine/irinotecan	Drug: Bevacizumab; Bevacizumab was administered as part of standard first-line treatment; Other Names: Avastin®
Bevacizumab and Fluorouracil +/- Folinic Acid; Participants who receive bevacizumab in combination with fluorouracil +/- folinic acid	Drug: Bevacizumab; Bevacizumab was administered as part of standard first-line treatment; Other Names: Avastin®; Drug: Fluorouracil +/- Folinic Acid; Fluorouracil +/- folinic acid were administered along with bevacizumab as part of standard first-line treatment
Other; Participants who receive bevacizumab in combination with other first-line chemotherapy regimens	Drug: Bevacizumab; Bevacizumab was administered as part of standard first-line treatment; Other Names: Avastin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Serious Adverse Events (SAEs)	An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires new in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes.	1.5 years
Percentage of Participants with Grade 3-5 Avastin Related Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. Adverse events were graded according to NCI-CTCAE, v4.0 (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0).	1.5 years
Progression-Free Survival	Progression-Free Survival (PFS) was defined as the number of days from start of first-line therapy administration (earliest date of either the start of chemotherapy regimen administration or the start of Avastin) to the date of first occurrence of investigator-assessed disease progression or death. PFS was assessed using Kaplan-Meier method.	1.5 years
Overall Survival	Overall Survival (OS) is defined as the number of days from the start of first-line therapy (earliest date of either the start of chemotherapy regimen administration or the start of Avastin) to death by any cause.	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Avastin Related Adverse Events of Special Interest	Adverse events of special interest (AESIs) are defined by their possible association with Avastin® treatment. The adverse events of special interest in this study include all grades of gastrointestinal perforation, fistulae, arterial and venous thromboembolic events, congestive heart failure and pulmonary haemorrhages; and Grade 2-5: hypertension, wound healing complications, proteinuria and mucocutaneous haemorrhages.	1.5 years
Reasons for Discontinuation of Avastin		1.5 years
Median Progression Free Survival from Four Avastin Studies	PFS was defined as the number of days from start of first-line therapy administration (earliest date of either the start of chemotherapy regimen administration or the start of Avastin) to the date of first occurrence of investigator-assessed disease progression or death. The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only. Median PFS is presented for data from other registration trials and similar observational studies.	1.5 years (ACORN)
Median Overall Survival from Four Avastin Studies	OS is defined as the number of days from the start of first-line therapy (earliest date of either the start of chemotherapy regimen administration or the start of Avastin) to death by any cause. The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only. Median OS is presented for data from other registration trials and similar observational studies.	1.5 years (ACORN)
Percentage of Participants with Comparative AEs from Four Avastin® Studies	Comparative AEs included Gastrointestinal perforation; Haemorrhage (specific grade); All Haemorrhages; Hypertension; and Arterial thromboembolic events (cerebrovascular accident, myocardial infarction, transient ischaemic attack and other). The specific grade of haemorrhage was 3/4 for BRITE, 3/4 for BEAT and 3-5 for ARIES. The specific grade for ACORN was unknown. The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	1.5 years (ACORN)
Median Age of Participants in Four Avastin® Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Percentage of Participants Over (or equal to) 75 Years of Age in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Percentage of Males and Females in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Eastern Cooperative Oncology Group (ECOG) Performance Status in Four Avastin Studies	ECOG Performance Status measured on-therapy (time between first dose and last dose date) assessed participant's performance status on 5 point scale: 0 is equal to (=) fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than [>] 50% of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead. The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	1.5 years (ACORN)
Race/Ethnicity of Participants in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Percentage of Participants at Stage IV (at diagnosis) in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Percentage of Participants that Received Previous Systematic Treatment for CRC in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Sites of CRC in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Percentage of Participants with Primary Resection in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Metastatic Sites of CRC in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Ongoing Patient Medical Conditions in Four Avastin Studies	The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.	Baseline
Weeks of Further Treatment After 1st Line Chemotherapy	Number of weeks of further chemotherapy regimen administered after 1st line treatment.	From disease progression until end of study.
Quality of Life as Assessed by the Euro-Quality of Life-5 Dimensions (EQ-5D) Weighted Index Score	The EQ-5D is composed of 5 single-item measures where participants responded to questions assessing health status by responding with either "no problems", "slight problems", "moderate problems", "severe problems" or "extreme [problem]/unable to perform" in the following categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Based on population surveys, an algorithm was used to combine the responses to each of these 5 measures into 1 single EQ-5D weighted index score ranging from -0.59 (extreme problems) to +1 (no problems) where a negative value indicated a worsening of perceived quality of life and a positive value indicated an improvement of perceived quality of life.	Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Quality of Life as Assessed by the Euro-Quality of Life-5 Dimensions (EQ-5D) Crosswalk Index Score	The EQ-5D is composed of 5 single-item measures where participants responded to questions assessing health status by responding with either "no problems", "slight problems", "moderate problems", "severe problems" or "extreme [problem]/unable to perform" in the following categories: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Based on population surveys, an algorithm was used to combine the responses to each of these 5 measures into 1 single EQ-5D index score ranging from -0.59 (extreme problems) to +1 (no problems) where a negative value indicated a worsening of perceived quality of life and a positive value indicated an improvement of perceived quality of life.	Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Response to the Burden of Illness Question: In the last three months how many times have health care professionals been to your home?		Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Response to the Burden of Illness Question: In the last three months how many times have you seen health care professionals at your GP Surgery or day centre?		Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Response to the Burden of Illness Question: In the last three months how many nights in total did you spend in hospital/hospice?		Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Response to the Burden of Illness Question: In the last three months how many times did you visit the imaging department for these examinations?		Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Response to the Burden of Illness Question: What was your employment status before diagnosis?		Baseline
Response to the Burden of Illness Question: What is your employment status now?		Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Response to the Burden of Illness Question: Has your cancer resulted in you seeking support services?		Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Response to the Burden of Illness Question: Has a previously employed family member had to take time off work to care for you?		Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy
Response to the Burden of Illness Question: Has your cancer resulted in a family member seeking support?		Baseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Khakoo S, Chau I, Pedley I, Ellis R, Steward W, Harrison M, Baijal S, Tahir S, Ross P, Raouf S, Ograbek A, Cunningham D; ACORN investigators. ACORN: Observational Study of Bevacizumab in Combination With First-Line Chemotherapy for Treatment of Metastatic Colorectal Cancer in the UK. Clin Colorectal Cancer. 2019 Dec;18(4):280-291.e5. doi: 10.1016/j.clcc.2019.07.003. Epub 2019 Jul 11.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2012
• Primary Completion (Actual): March 10, 2017
• Study Completion (Actual): March 10, 2017

Study Registration Dates

• First Submitted: January 5, 2012
• First Submitted That Met QC Criteria: January 5, 2012
• First Posted (Estimate): January 9, 2012

Study Record Updates

• Last Update Posted (Actual): May 14, 2018
• Last Update Submitted That Met QC Criteria: May 8, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Hematinics; Fluorouracil; Capecitabine; Oxaliplatin; Bevacizumab; Leucovorin; Irinotecan; Levoleucovorin; Folic Acid
• Other Study ID Numbers: ML27971

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No