Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Tubulin Modulators

Antimitotic Agents

bevacizumab [Avastin]

Standard chemotherapy

Clinical Trials

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.

A Study of Avastin (Bevacizumab) and Sequential Chemotherapy in Patients With Primary HER2 Negative Operable Breast Cancer.

An Open Label Study to Assess the Effect of a Combination of Avastin and Docetaxel and Sequential Chemotherapy on Pathological Response in Patients With Primary Operable HER2 Negative Breast Cancer

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.

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.

Breast-conserving surgery was defined as lumpectomy + lymphadenectomy (LA), segmentectomy + LA, quadrantectomy + LA, or other (including sentinal node extirpation tumorectomy).

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%).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

Hoffmann-La Roche

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.

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.

Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel

Age, Continuous

Female

Sex/Gender, Customized

Intent to Treat (ITT) Population: all participants included in the study.

Medical Communications

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.

Percentage of Participants With Pathological Complete Response (pCR)

CR+PR

CR+PR+NC

Percentage of Participants With Objective Clinical Response

ITT population; only those participants who underwent surgery were included in the analysis

Percentage of Participants With Breast-Conserving Surgery

High proliferative index (n=50)

Low proliferative index (n=15)

Population evaluable for anatomopathological response with evaluable levels of the specified biomarker; data were missing for 2 participants.

Percentage of Participants With pCR by Proliferation of Ki67

Anueploid (n=8)

Normal (n=13)

Amplification (n=2)

Only those participants evaluated for the specified biomarker were included in the analysis.

Percentage of Participants With pCR by Kisspeptin (KISS1) Amplification

No expression (n=18)

Normal (n=3)

Augmented expression (n=4)

Percentage of Participants With pCR by KISS1 Protein Expression

Anueploid (n=1)

Normal (n=18)

Amplification (n=4)

Percentage of Participants With pCR by Vascular Endothelial Growth Factor Receptor (VEGFR) Amplification

No expression (n=7)

Normal (n=5)

Augmented expression (n=10)

Percentage of Participants With pCR by VEGFR Protein Expression

No expression (n=25)

Normal (n=8)

Augmented expression (n=5)

Percentage of Participants With pCR by Hypoxia Inducible Factor (HIF) Protein Expression

No expression (n=24)

Normal (n=10)

Percentage of Participants With pCR by Endothelial Nitric Oxide Synthase (ENOS) Protein Expression

No expression (n=14)

Normal (n=1)

Augmented expression (n=11)

Percentage of Participants With pCR by Angiotension Protein Expression

Gene expression above housekeeping level (n=1)

Gene expression below housekeeping level (n=33)

Percentage of Participants With pCR by Vascular Endothelial Growth Factor (VEGF) Gene Expression

Gene expression above housekeeping level (n=7)

Gene expression below housekeeping level (n=27)

Percentage of Participants With pCR by VEGFR Gene Expression

Gene expression above housekeeping level (n=0)

Gene expression below housekeeping level (n=34)

Percentage of Participants With pCR by Phosphorylated AKT (pAKT) Gene Expression

Gene expression above housekeeping level (n=9)

Gene expression below housekeeping level (n=25)

Percentage of Participants With pCR by HIF Gene Expression

Percentage of Participants With pCR by Insulin-Like Growth Factor (IGF) Gene Expression

Percentage of Participants With pCR by ENOS Gene Expression

Gene expression above housekeeping level (n=30)

Gene expression equal to housekeeping level (n=1)

Gene expression below housekeeping level (n=3)

Percentage of Participants With pCR by Phosphorylated MAP Kinase (pMAPK) Gene Expression

Percentage of Participants With pCR by Angiotensin II Receptor Type I (AGTR) Gene Expression

Percentage of Participants With pCR by KISS1 Gene Expression

Percentage of Participants With pCR by RKISS1 Gene Expression

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.

Spots Global Cancer Trial Database for A Study of Avastin (Bevacizumab) and Sequential Chemotherapy in Patients With Primary HER2 Negative Operable Breast Cancer.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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