A Study of Avastin (Bevacizumab) Plus Herceptin (Trastuzumab) in Patients With Primary Inflammatory HER2-Positive Breast Cancer.
This study has been completed.
Information provided by (Responsible Party):
First received: July 16, 2008
Last updated: July 5, 2016
Last verified: July 2016
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.
|Breast Cancer||Drug: Standard chemotherapy Drug: bevacizumab [Avastin] Drug: trastuzumab [Herceptin]||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
Resource links provided by NLM:
U.S. FDA Resources
Further study details as provided by Hoffmann-La Roche:
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- 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.
|Study Start Date:||October 2008|
|Study Completion Date:||October 2014|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Drug: Standard chemotherapy
As prescribedDrug: bevacizumab [Avastin]
15mg/kg iv 3 weekly in cycles 1-8Drug: trastuzumab [Herceptin]
8mg/kg iv loading dose followed by 6mg/kg iv 3 weekly in cycles 5-8.
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: NCT00717405
Please refer to this study by its ClinicalTrials.gov identifier: NCT00717405
|Besancon, France, 25030|
|Bordeaux, France, 33000|
|Brest, France, 29609|
|Caen, France, 14076|
|Clermont Ferrand, France, 63011|
|Dijon, France, 21079|
|La Tronche, France, 38700|
|Lille, France, 59020|
|Lyon, France, 69373|
|Marseille, France, 13273|
|Montpellier, France, 34298|
|Nantes, France, 44202|
|Nice, France, 06189|
|Paris, France, 75231|
|Paris, France, 75475|
|Paris, France, 75970|
|Reims CEDEX, France, 51056|
|Rennes, France, 35042|
|Rouen, France, 76038|
|Saint Brieuc, France, 22015|
|Saint Herblain, France, 44805|
|St Cloud, France, 92210|
|St Priest En Jarez, France, 42271|
|Strasbourg, France, 67065|
|Strasbourg, France, 67098|
|Toulouse, France, 31059|
|Vandoeuvre Les Nancy, France, 54511|
|Villejuif, France, 94805|
Sponsors and Collaborators
|Study Director:||Clinical Trials||Hoffmann-La Roche|