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

Study Overview
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Brief Summary
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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.

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

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Capecitabine/Oxaliplatin
* Drug: Fluorouracil/Folinic Acid/Oxaliplatin
* Drug: Capecitabine
* Drug: Fluorouracil/Folinic Acid/Irinotecan
* Drug: Fluorouracil +/- Folinic Acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 |