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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01506167
• Other study ID #: ML27971
• Status: Completed
• Start date: July 6, 2012
• Est. completion date: March 10, 2017

Study information

• Verified date: May 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 719
• Est. completion date: March 10, 2017
• Est. primary completion date: March 10, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Bevacizumab
Bevacizumab was administered as part of standard first-line treatment
• Capecitabine/Oxaliplatin
Capecitabine/oxaliplatin were administered along with bevacizumab as part of standard first-line treatment
• Fluorouracil/Folinic Acid/Oxaliplatin
Fluorouracil/folinic acid/oxaliplatin were administered along with bevacizumab as part of standard first-line treatment
• Capecitabine
Capecitabine was administered along with bevacizumab as part of standard first-line treatment
• Fluorouracil/Folinic Acid/Irinotecan
Fluorouracil/folinic acid/irinotecan were administered along with bevacizumab as part of standard first-line treatment
• Fluorouracil +/- Folinic Acid
Fluorouracil +/- folinic acid were administered along with bevacizumab as part of standard first-line treatment

Locations

Country	Name	City	State
United Kingdom	Royal United Hospital Bath; Diabetes and Lipid Research, Wolfson Centre	Bath
United Kingdom	Wexham Park Hospital; Oncology	Berkshire
United Kingdom	Birmingham Heartlands Hospital; Dept of Oncology	Birmingham
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Bishop Auckland Hospital;Oncology Department	Bishop Auckland
United Kingdom	University Hospital of North Staffordhire	Blackpool
United Kingdom	Bradford Royal Infirmary; Dept of Medical Oncology C/O Ward15	Bradford
United Kingdom	Bristol Haematology and Oncology Centre	Bristol
United Kingdom	West Suffolk Hospital Nhs Trust; Gi Corridor	Bury St Edmunds
United Kingdom	Kent & Canterbury Hospital	Canterbury
United Kingdom	Cumberland Infirmary; Oncology Department	Carlisle
United Kingdom	Broomfield Hospital; Oncology	Chelsmford
United Kingdom	University Hospital North Tees	Cleveland
United Kingdom	Castle Hill Hospital; Academic Oncology	Cottingham
United Kingdom	Darlington Memorial Hospital	Darlington
United Kingdom	Russells Hall Hospital; Dept of Hematology	Dudley
United Kingdom	University Hospital of North Durham; Oncology	Durham
United Kingdom	Harrogate Hospital	Harrogate
United Kingdom	Northhwick Park Hospital;Oncology Department	Harrow
United Kingdom	Ipswich Hospital; Oncology Pharmacy	Ipswich
United Kingdom	Kidderminster Hospital; Oncology Dept	Kidderminster
United Kingdom	Guys Hosp./Med. Onc./3rd Fl. T; Clinical Trial Office	London
United Kingdom	Queen Elizabeth Hospital	London
United Kingdom	Royal Free Hospital; Dept of Oncology	London
United Kingdom	Macclesfield District General Hospital	Macclesfield
United Kingdom	Maidstone & Tonbridge Wells Hospital; Kent Oncology Center	Maidstone
United Kingdom	The James Cook University Hospital	Middlesborough
United Kingdom	Freeman Hospital	Newcastle upon Tyne
United Kingdom	North Tyneside General Hospital	North Shields
United Kingdom	Mount Vernon Cancer Centre	Northwood
United Kingdom	Nottingham University Hospitals City Campus	Nottingham
United Kingdom	Peterborough City Hospital, Edith Cavell Campus; Oncology Department	Peterborough
United Kingdom	Derriford Hospital; Gastroenterology	Plymouth
United Kingdom	Queen's Hospital	Romford
United Kingdom	Scunthorpe General Hospital; Dept of Oncology	Scunthorpe
United Kingdom	Stafford Hospital; Oncology Department	Stafford
United Kingdom	The Royal Marsden Hospital	Sutton
United Kingdom	Great Western Hospital, Swindon Cancer Research Unit; Osprey Unit Level 3	Swindon
United Kingdom	Torbay Hospital; Oncology	Torquay
United Kingdom	Royal Cornwall Hospital; Dept of Clinical Oncology	Truro
United Kingdom	Walsall Manor Hospital	Walsall
United Kingdom	Royal Hampshire County Hospital; Winchester & Andover Breast Unit	Winchester
United Kingdom	The Royal Wolverhampton Hospitals NHS Trust	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Reasons for Discontinuation of Avastin		1.5 years
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Response to the Burden of Illness Question: What was your employment status before diagnosis?		Baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	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