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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00559754
First received: November 15, 2007
Last updated: November 5, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: bevacizumab [Avastin]
Drug: Docetaxel
Drug: Standard chemotherapy
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Pathological Complete Response (pCR) [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Clinical Response [ Time Frame: Within 28 days of enrollment, Weeks 12 and 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Breast-Conserving Surgery [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Breast-conserving surgery was defined as lumpectomy + lymphadenectomy (LA), segmentectomy + LA, quadrantectomy + LA, or other (including sentinal node extirpation tumorectomy).

  • Percentage of Participants With pCR by Proliferation of Ki67 [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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%).

  • Percentage of Participants With pCR by Kisspeptin (KISS1) Amplification [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by KISS1 Protein Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Vascular Endothelial Growth Factor Receptor (VEGFR) Amplification [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by VEGFR Protein Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Hypoxia Inducible Factor (HIF) Protein Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Endothelial Nitric Oxide Synthase (ENOS) Protein Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Angiotension Protein Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Vascular Endothelial Growth Factor (VEGF) Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by VEGFR Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Phosphorylated AKT (pAKT) Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by HIF Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Insulin-Like Growth Factor (IGF) Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by ENOS Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Phosphorylated MAP Kinase (pMAPK) Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by Angiotensin II Receptor Type I (AGTR) Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by KISS1 Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With pCR by RKISS1 Gene Expression [ Time Frame: After Week 24 (surgery) ] [ Designated as safety issue: No ]
    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).


Enrollment: 72
Study Start Date: December 2007
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab [Avastin]
15mg/kg iv on day 1 of each 3 week cycle
Drug: Docetaxel
75mg/m2 iv on day 1 of each 3 week cycle
Drug: Standard chemotherapy
As prescribed

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00559754

Locations
Spain
Sabadell, Barcelona, Barcelona, Spain, 08208
Cordoba, Spain, 14004
Jaen, Spain, 23007
Lerida, Spain, 25198
Malaga, Spain, 29010
Zaragoza, Spain, 50009
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00559754     History of Changes
Other Study ID Numbers: ML20382
Study First Received: November 15, 2007
Results First Received: May 16, 2014
Last Updated: November 5, 2014
Health Authority: Spain: Agencia Espanola del medicamento (AEM)

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Docetaxel
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimitotic Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 19, 2014