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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00717405
• Other study ID #: ML21531
• Secondary ID: 2008-000783-16
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2008
• Last updated: December 1, 2015
• Start date: October 2008
• Est. completion date: October 2014

Study information

• Verified date: December 2015
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence francaise de securite sanitaire des produits de sante (AFSSAPS)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Standard chemotherapy
As prescribed
• bevacizumab [Avastin]
15mg/kg iv 3 weekly in cycles 1-8
• trastuzumab [Herceptin]
8mg/kg iv loading dose followed by 6mg/kg iv 3 weekly in cycles 5-8.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Breast Cancer Marker CA15.3 at Baseline, Neoadjuvant Final Visit and Change From Baseline at Neoadjuvant Final Visit		Baseline, Neoadjuvant Final Visit (Week 25)	No
Secondary	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	No
Secondary	Disease Free Survival (DFS) Duration	DFS was estimated using Kaplan-Meier method.	Up to 5 Years	No
Secondary	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	No
Secondary	Recurrence Free Survival (RFS) Duration	RFS was estimated using Kaplan-Meier method.	Up to 5 Years	No
Secondary	Percentage of Participants Who Were Alive at 3 and 5 Years		3, 5 years	No
Secondary	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	No