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A Study of Avastin (Bevacizumab) Plus Herceptin (Trastuzumab) in Patients With Primary Inflammatory HER2-Positive Breast Cancer.

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ClinicalTrials.gov Identifier: NCT00717405
Recruitment Status : Completed
First Posted : July 17, 2008
Results First Posted : January 6, 2016
Last Update Posted : August 2, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE July 16, 2008
First Posted Date  ICMJE July 17, 2008
Results First Submitted Date  ICMJE December 1, 2015
Results First Posted Date  ICMJE January 6, 2016
Last Update Posted Date August 2, 2016
Study Start Date  ICMJE October 2008
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 1, 2015)
Percentage of Participants With a Pathological Complete Response (PCR) According to the Sataloff Classification [ Time Frame: From baseline through Week 25 (Up to 6 months) ]
PCR was assessed at the time of definitive surgery according to Sataloff classification and centrally reviewed by an independent committee under blinded conditions. Pathological response was defined based on the therapeutic response at the primary tumor site and axillary lymph nodes. Primary tumor response criteria were as follows: T-A (Total / near total therapeutic effect), T-B (Subjectively greater than [>] 50 percent [%] therapeutic effect but less than [<] T-A), T-C (<50% therapeutic effect, but effect evident), T-D (No therapeutic effect). Axillary lymph node response: N-A (Evidence of therapeutic effect, no metastases), N-B (No therapeutic effect, no nodal metastases), N-C (Nodal metastasis but evident therapeutic effect), N-D (Nodal metastasis with no therapeutic effect). T-A and N-A or T-A and N-B responses were defined as PCR and all other tumor responses as non-responders. Participants with missing values were considered as non-responders.
Original Primary Outcome Measures  ICMJE
 (submitted: July 16, 2008)
Rate of pathological complete response [ Time Frame: Event driven ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2015)
  • Percentage of Participants With a PCR According to the Chevallier Classification [ Time Frame: From baseline through Week 25 (Up to 6 months) ]
    PCR was assessed at the time of definitive surgery according to Chevallier classification and centrally reviewed by an independent committee under blinded conditions. The Chevallier classification for grading of therapeutic effect related to the primary tumor site and axillary lymph nodes was defined by microscopic changes as follows - Grade 1: Disappearance of all tumors either in the breast or in the nodes, Grade 2: Persistence of carcinoma in situ in the breast only and no nodal invasion, Grade 3: Presence of invasive carcinoma with stromal alteration, Grade 4: Presence of invasive carcinoma without modification. Grade 1 response was considered as PCR. Participants with missing values were considered as non-responders.
  • Percentage of Participants Who Were Responders Based on Inflammatory Signs From Baseline at Cycle 5 and Final Treatment Visit [ Time Frame: Baseline, Cycle 5 (Week 15), Neo-adjuvant treatment final visit (Week 25) ]
    Breast tumor was physically evaluated during the study which included assessment for inflammatory signs and for overall clinical response. Participant with response from baseline based on inflammatory signs at Cycle 5 and final treatment visit were presented.
  • Percentage of Participants Who Were Responders Based on Overall Clinical Response From Baseline at Cycle 5 and Final Treatment Visit [ Time Frame: Baseline, Cycle 5 (Week 15), Neo-adjuvant treatment final visit (Week 25) ]
    Breast tumor was physically evaluated during the study which included assessment for inflammatory signs and for overall clinical response. Participant with response from baseline based on overall clinical response at Cycle 5 and final treatment visit were presented.
  • Number of Participants Who Underwent Mastectomy [ Time Frame: Anytime between Week 26 and Week 29 ]
    Surgery included a mastectomy with axillary node dissection and had to be performed at least 4 weeks after the last infusion of neoadjuvant bevacizumab treatment.
  • Percentage of Participants With Macroscopically Visible Tumor [ Time Frame: Anytime between Week 26 and Week 29 ]
    Local pathologists assessed the tumor whether it was macroscopically visible or not and percentage of participants for whom the tumor was macroscopically visible was reported.
  • Percentage of Participants Who Underwent Lymph Node Resection [ Time Frame: Anytime between Week 26 and Week 29 ]
    Among the participants who were planned to undergo mastectomy, lymph node resection was also performed by the physician depending up on the participant's breast cancer grades.
  • Breast Cancer Marker CA15.3 at Baseline, Neoadjuvant Final Visit and Change From Baseline at Neoadjuvant Final Visit [ Time Frame: Baseline, Neoadjuvant Final Visit (Week 25) ]
  • Percentage of Participants Who Were Disease Free at 3 and 5 Years [ Time Frame: 3, 5 years ]
    A participant was considered disease free if the participant did not experience any of the following events: local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colon carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause.
  • Disease Free Survival (DFS) Duration [ Time Frame: Up to 5 Years ]
    DFS was estimated using Kaplan-Meier method.
  • Percentage of Participants Who Were Recurrence Free at 3 and 5 Years [ Time Frame: 3, 5 years ]
    A participant was considered recurrence free if the participant did not experience local or regional recurrence (wall or axillaries nodes), or occurrence of distant metastases (including soft tissue and distal lymph nodes).
  • Recurrence Free Survival (RFS) Duration [ Time Frame: Up to 5 Years ]
    RFS was estimated using Kaplan-Meier method.
  • Percentage of Participants Who Were Alive at 3 and 5 Years [ Time Frame: 3, 5 years ]
  • Overall Survival (OS) Duration [ Time Frame: Up to 5 years ]
    OS was defined as the time from the first administration of neoadjuvant treatment to death of any cause. OS was estimated using Kaplan-Meier method.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2008)
  • Disease-free survival; recurrence free interval; overall survival. [ Time Frame: Event driven ]
  • AEs; cardiac safety [ Time Frame: Throughout study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Avastin (Bevacizumab) Plus Herceptin (Trastuzumab) in Patients With Primary Inflammatory HER2-Positive Breast Cancer.
Official Title  ICMJE An Open Label Study to Assess the Rate of Pathological Complete Response in Patients With Primary Inflammatory HER2-positive Breast Cancer Treated With Avastin + Herceptin Based Chemotherapy
Brief Summary This single arm study will assess the efficacy and safety of preoperative treatment with Avastin combined with Herceptin-based chemotherapy in patients with primary inflammatory HER2-positive breast cancer. Patients will be treated with a total of 8 cycles of pre-operative chemotherapy + Avastin + Herceptin. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Standard chemotherapy
    As prescribed
  • Drug: bevacizumab [Avastin]
    15mg/kg iv 3 weekly in cycles 1-8
  • Drug: trastuzumab [Herceptin]
    8mg/kg iv loading dose followed by 6mg/kg iv 3 weekly in cycles 5-8.
Study Arms  ICMJE Experimental: 1
Interventions:
  • Drug: Standard chemotherapy
  • Drug: bevacizumab [Avastin]
  • Drug: trastuzumab [Herceptin]
Publications * Pierga JY, Petit T, Delozier T, Ferrero JM, Campone M, Gligorov J, Lerebours F, Roché H, Bachelot T, Charafe-Jauffret E, Pavlyuk M, Kraemer S, Bidard FC, Viens P. Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol. 2012 Apr;13(4):375-84. doi: 10.1016/S1470-2045(12)70049-9. Epub 2012 Feb 28.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 16, 2010)
52
Original Estimated Enrollment  ICMJE
 (submitted: July 16, 2008)
50
Actual Study Completion Date  ICMJE October 2014
Actual Primary Completion Date April 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • adult females, >=18 years of age;
  • inflammatory breast cancer;
  • HER2-positive tumors;
  • performance status 0-2.

Exclusion Criteria:

  • metastases;
  • previous treatment with chemotherapy, radiation therapy or hormone therapy for a breast tumor;
  • clinically significant cardiovascular disease, or history of thrombotic disorders.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00717405
Other Study ID Numbers  ICMJE ML21531
2008-000783-16
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP