Trial Outcomes & Findings for A Study of Avastin (Bevacizumab) and Sequential Chemotherapy in Patients With Primary HER2 Negative Operable Breast Cancer. (NCT NCT00559754)
NCT ID: NCT00559754
Last Updated: 2014-11-10
Results Overview
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria: 1) the primary tumor was Grade 5 (no malignant cells identified at the location of the primary tumor (ductal carcinoma in situ may be present); 2) no involvement was identified in the lymph nodes; 3) the tumour size at evaluation of the surgical piece was 0 centimeters (cm); and 4) the pathological staging of the tumour from the surgical piece was pT0pN0pM0, the stage is not applicable (NA). It will only be considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes.
COMPLETED
PHASE2
72 participants
After Week 24 (surgery)
2014-11-10
Participant Flow
Participant milestones
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
Participants received doxorubicin 60 milligrams per square meter (mg/m\^2) intravenously (IV) followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
Participants then received bevacizumab 15 mg per kilogram (mg/kg) IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
|
Overall Study
STARTED
|
72
|
|
Overall Study
COMPLETED
|
61
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
Participants received doxorubicin 60 milligrams per square meter (mg/m\^2) intravenously (IV) followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
Participants then received bevacizumab 15 mg per kilogram (mg/kg) IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Overall Study
Disease progression
|
1
|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Investigator criteria
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
A Study of Avastin (Bevacizumab) and Sequential Chemotherapy in Patients With Primary HER2 Negative Operable Breast Cancer.
Baseline characteristics by cohort
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=72 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Age, Continuous
|
47.22 years
STANDARD_DEVIATION 9.85 • n=5 Participants
|
|
Sex/Gender, Customized
Female
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72 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After Week 24 (surgery)Population: Population evaluable for anatomopathological response: participants who satisfied all inclusion criteria and none of the exclusion criteria, received at least 2 cycles of chemotherapy treatment, and were evaluated pathologically.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria: 1) the primary tumor was Grade 5 (no malignant cells identified at the location of the primary tumor (ductal carcinoma in situ may be present); 2) no involvement was identified in the lymph nodes; 3) the tumour size at evaluation of the surgical piece was 0 centimeters (cm); and 4) the pathological staging of the tumour from the surgical piece was pT0pN0pM0, the stage is not applicable (NA). It will only be considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes.
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=66 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With Pathological Complete Response (pCR)
|
24.2 percentage of participants
Interval 14.5 to 36.4
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SECONDARY outcome
Timeframe: Within 28 days of enrollment, Weeks 12 and 24Population: ITT Population
Overall clinical response is the best response obtained through physical examination and/or radiological tests after completion of chemotherapy cycles. The percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) and was categorized as clinical response (CR+PR) or clinical benefit (CR+PR+ no change \[NC\]). Per RECIST, CR was defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. No unequivocal progression of non-target disease. No new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after the criteria for response were first met.
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=72 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With Objective Clinical Response
CR+PR
|
88.9 percentage of participants
Interval 79.3 to 95.1
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|
Percentage of Participants With Objective Clinical Response
CR+PR+NC
|
98.6 percentage of participants
Interval 92.5 to 99.9
|
SECONDARY outcome
Timeframe: Week 24Population: ITT population; only those participants who underwent surgery were included in the analysis
Breast-conserving surgery was defined as lumpectomy + lymphadenectomy (LA), segmentectomy + LA, quadrantectomy + LA, or other (including sentinal node extirpation tumorectomy).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=67 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With Breast-Conserving Surgery
|
62.7 percentage of participants
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SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Population evaluable for anatomopathological response with evaluable levels of the specified biomarker; data were missing for 2 participants.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. Biomarker Ki67 proliferation was defined as low (less than \[\<\]15% ) and high (≥15%).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=65 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With pCR by Proliferation of Ki67
High proliferative index (n=50)
|
24.0 percentage of participants
|
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Percentage of Participants With pCR by Proliferation of Ki67
Low proliferative index (n=15)
|
13.3 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. KISS1 amplification was defined as 1 (aneuploid), 2 (normal), 4 (amplification), or NE (not evaluated).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=23 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With pCR by Kisspeptin (KISS1) Amplification
Anueploid (n=8)
|
12.5 percentage of participants
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Percentage of Participants With pCR by Kisspeptin (KISS1) Amplification
Normal (n=13)
|
30.77 percentage of participants
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Percentage of Participants With pCR by Kisspeptin (KISS1) Amplification
Amplification (n=2)
|
50.0 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. KISS1 protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=25 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With pCR by KISS1 Protein Expression
No expression (n=18)
|
27.8 percentage of participants
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Percentage of Participants With pCR by KISS1 Protein Expression
Normal (n=3)
|
66.7 percentage of participants
|
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Percentage of Participants With pCR by KISS1 Protein Expression
Augmented expression (n=4)
|
50.0 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. VEFGR amplification was defined as 1 (aneuploid), 2 (normal), 4 (amplification), or NE (not evaluated).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=23 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With pCR by Vascular Endothelial Growth Factor Receptor (VEGFR) Amplification
Anueploid (n=1)
|
0 percentage of participants
|
|
Percentage of Participants With pCR by Vascular Endothelial Growth Factor Receptor (VEGFR) Amplification
Normal (n=18)
|
33.3 percentage of participants
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Percentage of Participants With pCR by Vascular Endothelial Growth Factor Receptor (VEGFR) Amplification
Amplification (n=4)
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. VEGFR protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=22 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With pCR by VEGFR Protein Expression
No expression (n=7)
|
28.6 percentage of participants
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Percentage of Participants With pCR by VEGFR Protein Expression
Normal (n=5)
|
40.0 percentage of participants
|
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Percentage of Participants With pCR by VEGFR Protein Expression
Augmented expression (n=10)
|
20.0 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. HIF protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=38 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With pCR by Hypoxia Inducible Factor (HIF) Protein Expression
No expression (n=25)
|
40.0 percentage of participants
|
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Percentage of Participants With pCR by Hypoxia Inducible Factor (HIF) Protein Expression
Normal (n=8)
|
12.5 percentage of participants
|
|
Percentage of Participants With pCR by Hypoxia Inducible Factor (HIF) Protein Expression
Augmented expression (n=5)
|
60.0 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. ENOS protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=38 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With pCR by Endothelial Nitric Oxide Synthase (ENOS) Protein Expression
No expression (n=24)
|
29.2 percentage of participants
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Percentage of Participants With pCR by Endothelial Nitric Oxide Synthase (ENOS) Protein Expression
Normal (n=10)
|
40.0 percentage of participants
|
|
Percentage of Participants With pCR by Endothelial Nitric Oxide Synthase (ENOS) Protein Expression
Augmented expression (n=4)
|
25.0 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. Angiotensin protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=26 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
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Percentage of Participants With pCR by Angiotension Protein Expression
No expression (n=14)
|
7.1 percentage of participants
|
|
Percentage of Participants With pCR by Angiotension Protein Expression
Normal (n=1)
|
0.0 percentage of participants
|
|
Percentage of Participants With pCR by Angiotension Protein Expression
Augmented expression (n=11)
|
63.6 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. VEGF gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
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|---|---|
|
Percentage of Participants With pCR by Vascular Endothelial Growth Factor (VEGF) Gene Expression
Gene expression above housekeeping level (n=1)
|
100.0 percentage of participants
|
|
Percentage of Participants With pCR by Vascular Endothelial Growth Factor (VEGF) Gene Expression
Gene expression below housekeeping level (n=33)
|
30.3 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. VEGFR gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by VEGFR Gene Expression
Gene expression above housekeeping level (n=7)
|
0.0 percentage of participants
|
|
Percentage of Participants With pCR by VEGFR Gene Expression
Gene expression below housekeeping level (n=27)
|
40.7 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. pAKT gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by Phosphorylated AKT (pAKT) Gene Expression
Gene expression above housekeeping level (n=0)
|
NA percentage of participants
No participants assessed had PAKT gene expression above the housekeeping level.
|
|
Percentage of Participants With pCR by Phosphorylated AKT (pAKT) Gene Expression
Gene expression below housekeeping level (n=34)
|
32.4 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. HIF gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by HIF Gene Expression
Gene expression above housekeeping level (n=9)
|
44.4 percentage of participants
|
|
Percentage of Participants With pCR by HIF Gene Expression
Gene expression below housekeeping level (n=25)
|
28.0 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. IGF gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by Insulin-Like Growth Factor (IGF) Gene Expression
Gene expression above housekeeping level (n=0)
|
NA percentage of participants
All participants assessed had IGF gene expression levels below the housekeeping level.
|
|
Percentage of Participants With pCR by Insulin-Like Growth Factor (IGF) Gene Expression
Gene expression below housekeeping level (n=34)
|
32.4 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. ENOS gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by ENOS Gene Expression
Gene expression above housekeeping level (n=1)
|
0 percentage of participants
|
|
Percentage of Participants With pCR by ENOS Gene Expression
Gene expression below housekeeping level (n=33)
|
33.3 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. pMAPK gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by Phosphorylated MAP Kinase (pMAPK) Gene Expression
Gene expression above housekeeping level (n=30)
|
33.3 percentage of participants
|
|
Percentage of Participants With pCR by Phosphorylated MAP Kinase (pMAPK) Gene Expression
Gene expression equal to housekeeping level (n=1)
|
0 percentage of participants
|
|
Percentage of Participants With pCR by Phosphorylated MAP Kinase (pMAPK) Gene Expression
Gene expression below housekeeping level (n=3)
|
33.3 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. AGTR gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=33 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by Angiotensin II Receptor Type I (AGTR) Gene Expression
Gene expression above housekeeping level (n=0)
|
NA percentage of participants
All participants had AGTR gene exptression below the housekeeping level.
|
|
Percentage of Participants With pCR by Angiotensin II Receptor Type I (AGTR) Gene Expression
Gene expression below housekeeping level (n=33)
|
30.3 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. KISS1 gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by KISS1 Gene Expression
Gene expression above housekeeping level (n=1)
|
0.0 percentage of participants
|
|
Percentage of Participants With pCR by KISS1 Gene Expression
Gene expression below housekeeping level (n=33)
|
33.3 percentage of participants
|
SECONDARY outcome
Timeframe: After Week 24 (surgery)Population: Only those participants evaluated for the specified biomarker were included in the analysis.
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. RKISS1 gene expression was defined as below the housekeeping reference level (\>0), above the housekeeping reference level (\<0), or equal to the housekeeping reference level (0).
Outcome measures
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=34 Participants
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Percentage of Participants With pCR by RKISS1 Gene Expression
Gene expression above housekeeping level (n=0)
|
NA percentage of participants
All participants had RKISS1 gene expression below the housekeeping level.
|
|
Percentage of Participants With pCR by RKISS1 Gene Expression
Gene expression below housekeeping level (n=34)
|
32.4 percentage of participants
|
Adverse Events
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
Serious adverse events
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=72 participants at risk
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Infections and infestations
Febrile neutropaenia
|
8.3%
6/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Infections and infestations
Infection with normal absolute neutrophil count (ANC) or grade 1 or 2 neutrophils
|
1.4%
1/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes
|
5.6%
4/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Mucositis/stomatitis
|
2.8%
2/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Vomiting
|
1.4%
1/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
Other adverse events
| Measure |
Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel
n=72 participants at risk
Participants received doxorubicin 60 mg/m\^2 IV followed by cyclophosphamide 600 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles. Participants then received bevacizumab 15 mg/kg IV followed by docetaxel 75 mg/m\^2 IV on Day 1, repeated every 3 weeks for a maximum of 4 cycles.
|
|---|---|
|
Gastrointestinal disorders
Mucositis/stomatitis
|
59.7%
43/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Nausea
|
59.7%
43/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
24/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Diarrhoea
|
23.6%
17/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Constipation
|
19.4%
14/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Taste alteration (dysgeusia)
|
8.3%
6/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Anorexia
|
6.9%
5/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Gastrointestinal disorders
Heartburn/dyspepsia
|
8.3%
6/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia
|
50.0%
36/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
16.7%
12/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Skin and subcutaneous tissue disorders
Rash: hand-foot skin reaction
|
5.6%
4/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Skin and subcutaneous tissue disorders
Other - not specified
|
5.6%
4/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
61.1%
44/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
General disorders
Fever
|
19.4%
14/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
General disorders
Other - not specified
|
6.9%
5/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
General disorders
Pain
|
50.0%
36/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes
|
13.9%
10/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
6.9%
5/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
5.6%
4/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Infections and infestations
Infection with normal ANC or grade 1 or 2 neutrophils
|
23.6%
17/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Infections and infestations
Febrile neutropaenia
|
5.6%
4/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
19.4%
14/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory
|
16.7%
12/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Eye disorders
Watery eye (epiphora, tearing)
|
9.7%
7/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Reproductive system and breast disorders
Irregular menses (change from baseline)
|
15.3%
11/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
5.6%
4/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
4/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Musculoskeletal and connective tissue disorders
Other - not specified
|
8.3%
6/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Renal and urinary disorders
Other - not specified
|
6.9%
5/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Cardiac disorders
Hypertension
|
9.7%
7/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
Endocrine disorders
Hot flashes/flushes
|
6.9%
5/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
|
General disorders
Flu-like syndrome
|
12.5%
9/72 • Adverse events (AEs) were reported from the day of informed consent to the last date of contact for all participants.
All enrolled participants who received at least 1 dose of study treatment. This study did not include a separate analysis of non-serious AEs therefore non-serious adverse events presented in this record include all adverse events reported during the study, not just non-serious events.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request the Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER