Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Bevacizumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Standard chemotherapy

bevacizumab [Avastin]

8mg/kg iv loading dose followed by 6mg/kg iv 3 weekly in cycles 5-8.

trastuzumab [Herceptin]

Clinical Trials

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

DFS was estimated using Kaplan-Meier method.

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).

RFS was estimated using Kaplan-Meier method.

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.

Hoffmann-La Roche

Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 mg/kg IV bevacizumab q3w for 8 cycles, 4 cycles of 500 mg/m\^2 IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.

Bevacizumab + Trastuzumab

Age, Continuous

Sex: Female, Male

Intent to treat population (ITT): Included all enrolled participants who had at least 1 post baseline assessment.

Medical Communications

Percentage of Participants With a Pathological Complete Response (PCR) According to the Sataloff Classification

Percentage of Participants With a PCR According to the Chevallier Classification

Response from baseline at Week 15 (n=43)

Response from baseline at Week 25 (n=42)

ITT population. Number of participants analyzed included participants for whom tumor physical examination was performed and were evaluated for response from baseline assessment of inflammatory signs. n included number of participants who were evaluable at a particular time point.

Percentage of Participants Who Were Responders Based on Inflammatory Signs From Baseline at Cycle 5 and Final Treatment Visit

Response from baseline at Week 15 (n=44)

Response from baseline at Week 25 (n=45)

ITT population. Number of participants analyzed included participants for whom tumor physical examination was performed. n included number of participants who were evaluable at a particular time point.

Percentage of Participants Who Were Responders Based on Overall Clinical Response From Baseline at Cycle 5 and Final Treatment Visit

Number of Participants Who Underwent Mastectomy

ITT population. Included participants who underwent mastectomy.

Percentage of Participants With Macroscopically Visible Tumor

Percentage of Participants Who Underwent Lymph Node Resection

Baseline (n=52)

Neoadjuvant final visit (n=37)

Change in CA15.3 at neoadjuvant final visit (n=37)

Safety population: Number of participants included all the participants who received at least one infusion of bevacizumab. n included participants who were evaluable at that time point.

Breast Cancer Marker CA15.3 at Baseline, Neoadjuvant Final Visit and Change From Baseline at Neoadjuvant Final Visit

3 years

5 years

Percentage of Participants Who Were Disease Free at 3 and 5 Years

Disease Free Survival (DFS) Duration

Percentage of Participants Who Were Recurrence Free at 3 and 5 Years

Recurrence Free Survival (RFS) Duration

Alive at 3 years

Alive at 5 years

Percentage of Participants Who Were Alive at 3 and 5 Years

Overall Survival (OS) Duration

Neoadjuvant treatment (Cycles 1-8, 3-week cycle): Participants received 15 milligrams per kilogram (mg/kg) intravenous (IV) bevacizumab every 3 weeks (q3w) for 8 cycles, 4 cycles of 500 milligrams per squared-meter (mg/m\^2) IV 5-fluorouracil, 100 mg/m\^2 IV epirubicin, and 500 mg/m\^2 IV cyclophosphamide, q3w, followed by 4 cycles of 100 mg/m\^2 IV docetaxel q3w plus trastuzumab (loading dose of 8 mg/kg and then 6 mg/kg q3w). Participants underwent surgery (mastectomy) after neoadjuvant treatment, maintaining trastuzumab (6 mg/kg). Adjuvant treatment: Participants received radiotherapy 2-4 weeks after surgery and lasted for 4-6 weeks, 6 mg/kg IV trastuzumab q3w and 15 mg/kg IV bevacizumab q3w administered along with/after the radiotherapy (administered up to a cumulative \[neoadjuvant + adjuvant\] total of 18 injections each. Hormonal therapy (at investigator discretion) after the end of radiotherapy was administered for 5 years, if participant was hormone receptor positive.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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