Trial Outcomes & Findings for Bevacizumab Given With Either Anastrozole or Fulvestrant With Trastuzumab for Postmenopausal Metastatic Breast Cancer (NCT NCT00405938)
NCT ID: NCT00405938
Last Updated: 2021-11-18
Results Overview
Progression Free Survival (PFS) is defined as the interval, in months, from the date of first treatment to the date of disease progression or death, whichever occurred first.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
79 participants
Primary outcome timeframe
18 months
Results posted on
2021-11-18
Participant Flow
Participant milestones
| Measure |
Bevacizumab/Anastrozole
Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] and anastrozole (1 mg orally daily). Treatment will be given in 4-week cycles.
|
Bevacizumab/Fulvestrant
Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] fulvestrant (500 mg intramuscular on Day 1 of Cycle 1, followed by 250 mg intramuscular of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg intramuscular of fulvestrant). Treatment will be given in 4-week cycles.
|
|---|---|---|
|
Overall Study
STARTED
|
38
|
41
|
|
Overall Study
COMPLETED
|
38
|
41
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bevacizumab Given With Either Anastrozole or Fulvestrant With Trastuzumab for Postmenopausal Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Bevacizumab/Anastrozole
n=38 Participants
Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] and anastrozole (1 mg orally daily). Treatment will be given in 4-week cycles.
|
Bevacizumab/Fulvestrant
n=41 Participants
Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] fulvestrant (500 mg intramuscular on Day 1 of Cycle 1, followed by 250 mg intramuscular of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg intramuscular of fulvestrant). Treatment will be given in 4-week cycles.
|
Total
n=79 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
n=5 Participants
|
63 years
n=7 Participants
|
63 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
38 participants
n=5 Participants
|
41 participants
n=7 Participants
|
79 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 monthsProgression Free Survival (PFS) is defined as the interval, in months, from the date of first treatment to the date of disease progression or death, whichever occurred first.
Outcome measures
| Measure |
Bevacizumab/Anastrozole
n=38 Participants
Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] and anastrozole (1 mg orally daily). Treatment will be given in 4-week cycles.
|
Bevacizumab/Fulvestrant
n=41 Participants
Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] fulvestrant (500 mg intramuscular on Day 1 of Cycle 1, followed by 250 mg intramuscular of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg intramuscular of fulvestrant). Treatment will be given in 4-week cycles.
|
|---|---|---|
|
Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
|
21 months
Interval 14.0 to
Upper limit not reached due to patients remaining on treatment at time of analysis.
|
9 months
Interval 5.0 to 13.0
|
SECONDARY outcome
Timeframe: 18 monthsThe Percentage of Patients Who Experience an Objective Benefit From Treatment (CR+PR). The response categories were assigned using RECIST criteria. Complete Response (CR) = Disappearance of all target lesions ; Partial Response (PR) = \>=30% decrease in the sum of the longest diameter of target lesions.
Outcome measures
| Measure |
Bevacizumab/Anastrozole
n=38 Participants
Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] and anastrozole (1 mg orally daily). Treatment will be given in 4-week cycles.
|
Bevacizumab/Fulvestrant
n=41 Participants
Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] fulvestrant (500 mg intramuscular on Day 1 of Cycle 1, followed by 250 mg intramuscular of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg intramuscular of fulvestrant). Treatment will be given in 4-week cycles.
|
|---|---|---|
|
Objective Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
|
18 Participants
|
11 Participants
|
Adverse Events
Bevacizumab/Anastrozole
Serious events: 10 serious events
Other events: 38 other events
Deaths: 0 deaths
Bevacizumab/Fulvestrant
Serious events: 12 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Bevacizumab/Anastrozole
n=38 participants at risk
Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] and anastrozole (1 mg orally daily). Treatment will be given in 4-week cycles.
|
Bevacizumab/Fulvestrant
n=41 participants at risk
Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] fulvestrant (500 mg intramuscular on Day 1 of Cycle 1, followed by 250 mg intramuscular of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg intramuscular of fulvestrant). Treatment will be given in 4-week cycles.
|
|---|---|---|
|
Nervous system disorders
Syncope
|
0.00%
0/38
|
2.4%
1/41 • Number of events 2
|
|
Cardiac disorders
cTnI
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Cardiac disorders
Superventricular Arrhythmia - Sinus Bradycardia
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.9%
3/38 • Number of events 3
|
0.00%
0/41
|
|
Infections and infestations
Infection - Pneumonia
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Dehydration
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Renal and urinary disorders
Renal Failure
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Failure to Thrive
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
Seizure
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Cardiac disorders
Pain - Cardiac
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Psychiatric disorders
Mood Alteration - Depression
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Vascular disorders
Thrombosis/Thrombus/Embolism
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
Diarrhea
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
ARDS
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Nervous system disorders
CNS Ischemia
|
2.6%
1/38 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Cardiac disorders
Cardiac Ischemia/Infarction
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Infections and infestations
Infection - Wound
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Surgical and medical procedures
Pain - Abdomen
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Death
|
0.00%
0/38
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Weakness
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Cardiac disorders
Restrictive Cardiomyopathy
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
|
Metabolism and nutrition disorders
Hypernatremia
|
2.6%
1/38 • Number of events 1
|
0.00%
0/41
|
Other adverse events
| Measure |
Bevacizumab/Anastrozole
n=38 participants at risk
Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] and anastrozole (1 mg orally daily). Treatment will be given in 4-week cycles.
|
Bevacizumab/Fulvestrant
n=41 participants at risk
Bevacizumab/fulvestrant (with trastuzumab in HER2+ patients). Bevacizumab 10mg/kg IV every 2 weeks \[patients who are also receiving trastuzumab have the option to receive their bevacizumab at 15 mg/kg every 3 weeks instead of 10 mg/kg every 2 weeks (see Trastuzumab section below)\] fulvestrant (500 mg intramuscular on Day 1 of Cycle 1, followed by 250 mg intramuscular of fulvestrant on Day 15 of Cycle 1. On Day 1 of Cycle 2 and the first day of all subsequent cycles thereafter, patients in this treatment arm will receive 250 mg intramuscular of fulvestrant). Treatment will be given in 4-week cycles.
|
|---|---|---|
|
Gastrointestinal disorders
Anorexia
|
18.4%
7/38 • Number of events 23
|
17.1%
7/41 • Number of events 27
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
34.2%
13/38 • Number of events 121
|
24.4%
10/41 • Number of events 34
|
|
Skin and subcutaneous tissue disorders
Bruising
|
0.00%
0/38
|
7.3%
3/41 • Number of events 3
|
|
Metabolism and nutrition disorders
AST
|
5.3%
2/38 • Number of events 4
|
0.00%
0/41
|
|
Metabolism and nutrition disorders
Bilirubin
|
5.3%
2/38 • Number of events 3
|
0.00%
0/41
|
|
Cardiac disorders
Cardiac Genral, Other (Decreased LVEF)
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
|
Nervous system disorders
Confusion
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
|
Gastrointestinal disorders
Constipation
|
13.2%
5/38 • Number of events 11
|
17.1%
7/41 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.4%
7/38 • Number of events 10
|
19.5%
8/41 • Number of events 29
|
|
Metabolism and nutrition disorders
Creatinine
|
0.00%
0/38
|
7.3%
3/41 • Number of events 20
|
|
Gastrointestinal disorders
Dehydration
|
5.3%
2/38 • Number of events 2
|
12.2%
5/41 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhea
|
23.7%
9/38 • Number of events 18
|
22.0%
9/41 • Number of events 12
|
|
Nervous system disorders
Dizziness
|
10.5%
4/38 • Number of events 9
|
22.0%
9/41 • Number of events 22
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
15.8%
6/38 • Number of events 9
|
22.0%
9/41 • Number of events 13
|
|
Blood and lymphatic system disorders
Edema - Limb
|
13.2%
5/38 • Number of events 46
|
17.1%
7/41 • Number of events 33
|
|
Blood and lymphatic system disorders
Edema - NOS
|
7.9%
3/38 • Number of events 23
|
0.00%
0/41
|
|
General disorders
Fatigue
|
57.9%
22/38 • Number of events 168
|
73.2%
30/41 • Number of events 170
|
|
General disorders
Fever
|
10.5%
4/38 • Number of events 4
|
7.3%
3/41 • Number of events 5
|
|
General disorders
Pain - Head
|
44.7%
17/38 • Number of events 53
|
7.3%
3/41 • Number of events 3
|
|
Gastrointestinal disorders
Heartburn
|
10.5%
4/38 • Number of events 17
|
17.1%
7/41 • Number of events 27
|
|
Blood and lymphatic system disorders
Hemoglobin
|
34.2%
13/38 • Number of events 57
|
29.3%
12/41 • Number of events 44
|
|
Blood and lymphatic system disorders
Hemorrhage - Nose
|
21.1%
8/38 • Number of events 14
|
24.4%
10/41 • Number of events 21
|
|
Gastrointestinal disorders
Hemorrhoids
|
5.3%
2/38 • Number of events 10
|
0.00%
0/41
|
|
Endocrine disorders
Hot Flashes
|
34.2%
13/38 • Number of events 51
|
19.5%
8/41 • Number of events 23
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
7.9%
3/38 • Number of events 8
|
7.3%
3/41 • Number of events 5
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.9%
3/38 • Number of events 7
|
7.3%
3/41 • Number of events 7
|
|
Cardiac disorders
Hypertension
|
47.4%
18/38 • Number of events 70
|
48.8%
20/41 • Number of events 110
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/38
|
7.3%
3/41 • Number of events 3
|
|
Cardiac disorders
Hypotension
|
0.00%
0/38
|
12.2%
5/41 • Number of events 6
|
|
Infections and infestations
Infection - Dental
|
0.00%
0/38
|
7.3%
3/41 • Number of events 6
|
|
Infections and infestations
Infection - Ear
|
5.3%
2/38 • Number of events 6
|
0.00%
0/41
|
|
Infections and infestations
Infection - Sinus
|
10.5%
4/38 • Number of events 16
|
9.8%
4/41 • Number of events 5
|
|
Infections and infestations
Infection - Skin
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
|
Infections and infestations
Infection - Bladder
|
15.8%
6/38 • Number of events 9
|
7.3%
3/41 • Number of events 6
|
|
Infections and infestations
Infection - Pulmonary
|
10.5%
4/38 • Number of events 5
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Injection Site Reaction
|
0.00%
0/38
|
7.3%
3/41 • Number of events 3
|
|
General disorders
Insomnia
|
13.2%
5/38 • Number of events 13
|
9.8%
4/41 • Number of events 10
|
|
Blood and lymphatic system disorders
Leukopenia
|
13.2%
5/38 • Number of events 13
|
19.5%
8/41 • Number of events 19
|
|
Blood and lymphatic system disorders
Lymphedema
|
5.3%
2/38 • Number of events 7
|
0.00%
0/41
|
|
Psychiatric disorders
Mood Alteration - Anxiety
|
13.2%
5/38 • Number of events 18
|
14.6%
6/41 • Number of events 18
|
|
Psychiatric disorders
Mood Alteration - Depression
|
10.5%
4/38 • Number of events 19
|
9.8%
4/41 • Number of events 26
|
|
Psychiatric disorders
Mood Alteration - NOS
|
7.9%
3/38 • Number of events 11
|
0.00%
0/41
|
|
Gastrointestinal disorders
Mucositis/Stomatitis
|
10.5%
4/38 • Number of events 4
|
17.1%
7/41 • Number of events 20
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.5%
4/38 • Number of events 9
|
12.2%
5/41 • Number of events 14
|
|
Gastrointestinal disorders
Nausea
|
36.8%
14/38 • Number of events 48
|
29.3%
12/41 • Number of events 44
|
|
Nervous system disorders
Neuropathy - Motor
|
5.3%
2/38 • Number of events 5
|
0.00%
0/41
|
|
Nervous system disorders
Neuropathy - Sensory
|
18.4%
7/38 • Number of events 12
|
22.0%
9/41 • Number of events 15
|
|
Blood and lymphatic system disorders
Neutrophils
|
5.3%
2/38 • Number of events 46
|
7.3%
3/41 • Number of events 4
|
|
General disorders
Pain - Abdomen
|
10.5%
4/38 • Number of events 22
|
0.00%
0/41
|
|
General disorders
Pain - Back
|
21.1%
8/38 • Number of events 39
|
29.3%
12/41 • Number of events 24
|
|
General disorders
Pain - Bladder
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
|
General disorders
Pain - Bone
|
10.5%
4/38 • Number of events 9
|
17.1%
7/41 • Number of events 61
|
|
General disorders
Pain - Breast
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
|
General disorders
Pain - Chest Wall
|
15.8%
6/38 • Number of events 6
|
12.2%
5/41 • Number of events 12
|
|
General disorders
Pain - Ear
|
5.3%
2/38 • Number of events 6
|
0.00%
0/41
|
|
General disorders
Pain - Joint
|
28.9%
11/38 • Number of events 37
|
24.4%
10/41 • Number of events 28
|
|
General disorders
Pain - Limb
|
34.2%
13/38 • Number of events 81
|
29.3%
12/41 • Number of events 32
|
|
General disorders
Pain - Muscle
|
10.5%
4/38 • Number of events 10
|
7.3%
3/41 • Number of events 9
|
|
General disorders
Pain - Neck
|
7.9%
3/38 • Number of events 24
|
0.00%
0/41
|
|
General disorders
Pain - NOS
|
5.3%
2/38 • Number of events 9
|
0.00%
0/41
|
|
General disorders
Pain - Pelvis
|
0.00%
0/38
|
7.3%
3/41 • Number of events 10
|
|
Blood and lymphatic system disorders
Platelets
|
21.1%
8/38 • Number of events 41
|
9.8%
4/41 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
|
Metabolism and nutrition disorders
Proteinuria
|
34.2%
13/38 • Number of events 97
|
43.9%
18/41 • Number of events 91
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
7.9%
3/38 • Number of events 3
|
0.00%
0/41
|
|
Skin and subcutaneous tissue disorders
Rash/Desquamation
|
10.5%
4/38 • Number of events 14
|
12.2%
5/41 • Number of events 6
|
|
Renal and urinary disorders
Renal Insufficiency
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis
|
23.7%
9/38 • Number of events 32
|
17.1%
7/41 • Number of events 38
|
|
General disorders
Rigor/Chills
|
5.3%
2/38 • Number of events 2
|
7.3%
3/41 • Number of events 8
|
|
Gastrointestinal disorders
Taste Alteration
|
7.9%
3/38 • Number of events 20
|
0.00%
0/41
|
|
General disorders
Sweating
|
0.00%
0/38
|
9.8%
4/41 • Number of events 11
|
|
Vascular disorders
Thrombosis/Thrombus/Embolism
|
5.3%
2/38 • Number of events 13
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
Voice Changes
|
0.00%
0/38
|
12.2%
5/41 • Number of events 28
|
|
Gastrointestinal disorders
Vomiting
|
18.4%
7/38 • Number of events 14
|
12.2%
5/41 • Number of events 7
|
|
General disorders
Weakness
|
13.2%
5/38 • Number of events 11
|
0.00%
0/41
|
|
Metabolism and nutrition disorders
Weight Loss
|
10.5%
4/38 • Number of events 32
|
7.3%
3/41 • Number of events 4
|
|
Surgical and medical procedures
Wound Complication
|
5.3%
2/38 • Number of events 2
|
0.00%
0/41
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
- Publication restrictions are in place
Restriction type: OTHER