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

Completed
Conditions
Colorectal Cancer
Interventions
Drug: Bevacizumab
Drug: Capecitabine/Oxaliplatin
Drug: Fluorouracil/Folinic Acid/Oxaliplatin
Drug: Fluorouracil/Folinic Acid/Irinotecan
Drug: Fluorouracil +/- Folinic Acid
Drug: Capecitabine
Registration Number
NCT01506167
Lead Sponsor
Hoffmann-La Roche
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
719
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
Read More
Exclusion Criteria
  • Investigational, non-standard of care first-line chemotherapy regimen for treatment of metastatic colorectal cancer
  • Contraindication to Avastin
Read More

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Bevacizumab and Capecitabine/OxaliplatinBevacizumabParticipants who receive bevacizumab in combination with capecitabine/oxaliplatin
Bevacizumab and Capecitabine/OxaliplatinCapecitabine/OxaliplatinParticipants who receive bevacizumab in combination with capecitabine/oxaliplatin
Bevacizumab and Fluorouracil/Folinic Acid/OxaliplatinBevacizumabParticipants who receive bevacizumab in combination with fluorouracil/folinic acid/oxaliplatin
Bevacizumab and Fluorouracil/Folinic Acid/OxaliplatinFluorouracil/Folinic Acid/OxaliplatinParticipants who receive bevacizumab in combination with fluorouracil/folinic acid/oxaliplatin
Bevacizumab and Fluorouracil/Folinic Acid/IrinotecanFluorouracil/Folinic Acid/IrinotecanParticipants who receive bevacizumab in combination with fluorouracil/folinic acid/irinotecan
Bevacizumab and Capecitabine/IrinotecanBevacizumabParticipants who receive bevacizumab in combination with capecitabine/irinotecan
Bevacizumab and Fluorouracil +/- Folinic AcidBevacizumabParticipants who receive bevacizumab in combination with fluorouracil +/- folinic acid
Bevacizumab and Fluorouracil +/- Folinic AcidFluorouracil +/- Folinic AcidParticipants who receive bevacizumab in combination with fluorouracil +/- folinic acid
Bevacizumab and CapecitabineBevacizumabParticipants who receive bevacizumab in combination with capecitabine
Bevacizumab and CapecitabineCapecitabineParticipants who receive bevacizumab in combination with capecitabine
Bevacizumab and Fluorouracil/Folinic Acid/IrinotecanBevacizumabParticipants who receive bevacizumab in combination with fluorouracil/folinic acid/irinotecan
OtherBevacizumabParticipants who receive bevacizumab in combination with other first-line chemotherapy regimens
Primary Outcome Measures
NameTimeMethod
Percentage of Participants with Serious Adverse Events (SAEs)1.5 years

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.

Percentage of Participants with Grade 3-5 Avastin Related Adverse Events1.5 years

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).

Progression-Free Survival1.5 years

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.

Overall Survival1.5 years

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.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants with Avastin Related Adverse Events of Special Interest1.5 years

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.

Reasons for Discontinuation of Avastin1.5 years
Median Progression Free Survival from Four Avastin Studies1.5 years (ACORN)

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.

Median Overall Survival from Four Avastin Studies1.5 years (ACORN)

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.

Percentage of Participants with Comparative AEs from Four Avastin® Studies1.5 years (ACORN)

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.

Median Age of Participants in Four Avastin® StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Percentage of Participants Over (or equal to) 75 Years of Age in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Percentage of Males and Females in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Eastern Cooperative Oncology Group (ECOG) Performance Status in Four Avastin Studies1.5 years (ACORN)

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.

Race/Ethnicity of Participants in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Percentage of Participants at Stage IV (at diagnosis) in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Percentage of Participants that Received Previous Systematic Treatment for CRC in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Sites of CRC in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Percentage of Participants with Primary Resection in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Metastatic Sites of CRC in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Ongoing Patient Medical Conditions in Four Avastin StudiesBaseline

The BRITE, BEAT and ARIES trials were conducted outside of the UK unlike the ACORN trial which was conducted in England only.

Weeks of Further Treatment After 1st Line ChemotherapyFrom disease progression until end of study.

Number of weeks of further chemotherapy regimen administered after 1st line treatment.

Quality of Life as Assessed by the Euro-Quality of Life-5 Dimensions (EQ-5D) Weighted Index ScoreBaseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy

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.

Quality of Life as Assessed by the Euro-Quality of Life-5 Dimensions (EQ-5D) Crosswalk Index ScoreBaseline and 3, 6, 9, 12, 15, 18, 21, 24 and 27 Months post chemotherapy

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.

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

Trial Locations

Locations (42)

Walsall Manor Hospital

🇬🇧

Walsall, United Kingdom

University Hospital of North Staffordhire

🇬🇧

Blackpool, United Kingdom

Royal United Hospital Bath; Diabetes and Lipid Research, Wolfson Centre

🇬🇧

Bath, United Kingdom

Bishop Auckland Hospital;Oncology Department

🇬🇧

Bishop Auckland, United Kingdom

West Suffolk Hospital Nhs Trust; Gi Corridor

🇬🇧

Bury St Edmunds, United Kingdom

Castle Hill Hospital; Academic Oncology

🇬🇧

Cottingham, United Kingdom

Kent & Canterbury Hospital

🇬🇧

Canterbury, United Kingdom

Queen Elizabeth Hospital

🇬🇧

London, United Kingdom

Wexham Park Hospital; Oncology

🇬🇧

Berkshire, United Kingdom

Darlington Memorial Hospital

🇬🇧

Darlington, United Kingdom

Harrogate Hospital

🇬🇧

Harrogate, United Kingdom

Birmingham Heartlands Hospital; Dept of Oncology

🇬🇧

Birmingham, United Kingdom

Northhwick Park Hospital;Oncology Department

🇬🇧

Harrow, United Kingdom

Russells Hall Hospital; Dept of Hematology

🇬🇧

Dudley, United Kingdom

Bristol Haematology and Oncology Centre

🇬🇧

Bristol, United Kingdom

Bradford Royal Infirmary; Dept of Medical Oncology C/O Ward15

🇬🇧

Bradford, United Kingdom

Cumberland Infirmary; Oncology Department

🇬🇧

Carlisle, United Kingdom

Broomfield Hospital; Oncology

🇬🇧

Chelsmford, United Kingdom

University Hospital North Tees

🇬🇧

Cleveland, United Kingdom

Ipswich Hospital; Oncology Pharmacy

🇬🇧

Ipswich, United Kingdom

Kidderminster Hospital; Oncology Dept

🇬🇧

Kidderminster, United Kingdom

Royal Free Hospital; Dept of Oncology

🇬🇧

London, United Kingdom

Guys Hosp./Med. Onc./3rd Fl. T; Clinical Trial Office

🇬🇧

London, United Kingdom

Mount Vernon Cancer Centre

🇬🇧

Northwood, United Kingdom

Maidstone & Tonbridge Wells Hospital; Kent Oncology Center

🇬🇧

Maidstone, United Kingdom

Macclesfield District General Hospital

🇬🇧

Macclesfield, United Kingdom

Peterborough City Hospital, Edith Cavell Campus; Oncology Department

🇬🇧

Peterborough, United Kingdom

Derriford Hospital; Gastroenterology

🇬🇧

Plymouth, United Kingdom

Freeman Hospital

🇬🇧

Newcastle upon Tyne, United Kingdom

North Tyneside General Hospital

🇬🇧

North Shields, United Kingdom

The James Cook University Hospital

🇬🇧

Middlesborough, United Kingdom

Nottingham University Hospitals City Campus

🇬🇧

Nottingham, United Kingdom

Scunthorpe General Hospital; Dept of Oncology

🇬🇧

Scunthorpe, United Kingdom

Stafford Hospital; Oncology Department

🇬🇧

Stafford, United Kingdom

Queen's Hospital

🇬🇧

Romford, United Kingdom

The Royal Marsden Hospital

🇬🇧

Sutton, United Kingdom

Torbay Hospital; Oncology

🇬🇧

Torquay, United Kingdom

Royal Cornwall Hospital; Dept of Clinical Oncology

🇬🇧

Truro, United Kingdom

The Royal Wolverhampton Hospitals NHS Trust

🇬🇧

Wolverhampton, United Kingdom

Royal Hampshire County Hospital; Winchester & Andover Breast Unit

🇬🇧

Winchester, United Kingdom

University Hospital of North Durham; Oncology

🇬🇧

Durham, United Kingdom

Great Western Hospital, Swindon Cancer Research Unit; Osprey Unit Level 3

🇬🇧

Swindon, United Kingdom

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