This single arm study will assess the efficacy and safety of a combination of Avastin and docetaxel following cyclophosphamide and doxorubicin, in patients with HER2 negative operable breast cancer. Patients will receive 4 x 3 week cycles of chemotherapy with doxorubicin (60mg/m2 iv on day 1 of each cycle) and cyclophosphamide (600mg/m2 iv on day 1 of each cycle). They will then receive 4 x 3 week cycles of docetaxel (75mg/m2 on day 1 of each cycle) in combination with Avastin (15mg/kg on day 1 of each cycle). The anticipated time on study treatment is 3-12 months, and the target sample size is \<100 individuals.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
72
15mg/kg iv on day 1 of each 3 week cycle
75mg/m2 iv on day 1 of each 3 week cycle
As prescribed
Unnamed facility
Sabadell, Barcelona, Barcelona, Spain
Unnamed facility
Córdoba, Cordoba, Spain
Unnamed facility
Jaén, Jaen, Spain
Unnamed facility
Lleida, Lerida, Spain
Unnamed facility
Málaga, Malaga, Spain
Unnamed facility
Zaragoza, Zaragoza, Spain
Percentage of Participants With Pathological Complete Response (pCR)
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.
Time frame: After Week 24 (surgery)
Percentage of Participants With Objective Clinical Response
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.
Time frame: Within 28 days of enrollment, Weeks 12 and 24
Percentage of Participants With Breast-Conserving Surgery
Breast-conserving surgery was defined as lumpectomy + lymphadenectomy (LA), segmentectomy + LA, quadrantectomy + LA, or other (including sentinal node extirpation tumorectomy).
Time frame: Week 24
Percentage of Participants With pCR by Proliferation of Ki67
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%).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Kisspeptin (KISS1) Amplification
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by KISS1 Protein Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Vascular Endothelial Growth Factor Receptor (VEGFR) Amplification
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by VEGFR Protein Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Hypoxia Inducible Factor (HIF) Protein Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Endothelial Nitric Oxide Synthase (ENOS) Protein Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Angiotension Protein Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Vascular Endothelial Growth Factor (VEGF) Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by VEGFR Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Phosphorylated AKT (pAKT) Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by HIF Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Insulin-Like Growth Factor (IGF) Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by ENOS Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Phosphorylated MAP Kinase (pMAPK) Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by Angiotensin II Receptor Type I (AGTR) Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by KISS1 Gene Expression
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).
Time frame: After Week 24 (surgery)
Percentage of Participants With pCR by RKISS1 Gene Expression
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).
Time frame: After Week 24 (surgery)
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