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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00559754
• Other study ID #: ML20382
• Status: Completed
• Phase: Phase 2
• First received: November 15, 2007
• Last updated: November 5, 2014
• Start date: December 2007
• Est. completion date: September 2010

Study information

• Verified date: November 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Espanola del medicamento (AEM)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• female patients, >=18 years of age;

• primary HER2-negative operable breast cancer;

• tumor >2cm in size;

• ECOG performance status 0-1.

Exclusion Criteria:

• previous treatment for breast cancer;

• metastatic disease;

• current or recent (within 10 days of first dose of Avastin) use of aspirin (>325mg/day) or full-dose anticoagulants for therapeutic purposes;

• clinically significant cardiovascular disease.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• bevacizumab [Avastin]
15mg/kg iv on day 1 of each 3 week cycle
• Docetaxel
75mg/m2 iv on day 1 of each 3 week cycle
• Standard chemotherapy
As prescribed

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	After Week 24 (surgery)	No
Secondary	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.	Within 28 days of enrollment, Weeks 12 and 24	No
Secondary	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).	Week 24	No
Secondary	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%).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No
Secondary	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).	After Week 24 (surgery)	No