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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Standard chemotherapy
* Drug: bevacizumab [Avastin]
* Drug: trastuzumab [Herceptin]


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Standard chemotherapy<br>* As prescribed<br>Drug: bevacizumab [Avastin]<br>* 15mg/kg iv 3 weekly in cycles 1-8<br>Drug: trastuzumab [Herceptin]<br>* 8mg/kg iv loading dose followed by 6mg/kg iv 3 weekly in cycles 5-8.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Pathological Complete Response (PCR) According to the Sataloff Classification | 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. | From baseline through Week 25 (Up to 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a PCR According to the Chevallier Classification | 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. | From baseline through Week 25 (Up to 6 months) | 
| Percentage of Participants Who Were Responders Based on Inflammatory Signs From Baseline at Cycle 5 and Final Treatment Visit | 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. | Baseline, Cycle 5 (Week 15), Neo-adjuvant treatment final visit (Week 25) | 
| Percentage of Participants Who Were Responders Based on Overall Clinical Response From Baseline at Cycle 5 and Final Treatment Visit | 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. | Baseline, Cycle 5 (Week 15), Neo-adjuvant treatment final visit (Week 25) | 
| Number of Participants Who Underwent Mastectomy | 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. | Anytime between Week 26 and Week 29 | 
| Percentage of Participants With Macroscopically Visible Tumor | 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. | Anytime between Week 26 and Week 29 | 
| Percentage of Participants Who Underwent Lymph Node Resection | 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. | Anytime between Week 26 and Week 29 | 
| Breast Cancer Marker CA15.3 at Baseline, Neoadjuvant Final Visit and Change From Baseline at Neoadjuvant Final Visit |  | Baseline, Neoadjuvant Final Visit (Week 25) | 
| Percentage of Participants Who Were Disease Free at 3 and 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. | 3, 5 years | 
| Disease Free Survival (DFS) Duration | DFS was estimated using Kaplan-Meier method. | Up to 5 Years | 
| Percentage of Participants Who Were Recurrence Free at 3 and 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). | 3, 5 years | 
| Recurrence Free Survival (RFS) Duration | RFS was estimated using Kaplan-Meier method. | Up to 5 Years | 
| Percentage of Participants Who Were Alive at 3 and 5 Years |  | 3, 5 years | 
| Overall Survival (OS) Duration | 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. | Up to 5 years |