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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00717405
First received: July 16, 2008
Last updated: December 1, 2015
Last verified: December 2015
  Purpose
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.

Condition Intervention Phase
Breast Cancer
Drug: Standard chemotherapy
Drug: bevacizumab [Avastin]
Drug: trastuzumab [Herceptin]
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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:


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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Were Disease Free at 3 and 5 Years [ Time Frame: 3, 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    DFS was estimated using Kaplan-Meier method.

  • Percentage of Participants Who Were Recurrence Free at 3 and 5 Years [ Time Frame: 3, 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    RFS was estimated using Kaplan-Meier method.

  • Percentage of Participants Who Were Alive at 3 and 5 Years [ Time Frame: 3, 5 years ] [ Designated as safety issue: No ]
  • Overall Survival (OS) Duration [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 52
Study Start Date: October 2008
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  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

Locations
France
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
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00717405     History of Changes
Other Study ID Numbers: ML21531  2008-000783-16 
Study First Received: July 16, 2008
Results First Received: December 1, 2015
Last Updated: December 1, 2015
Health Authority: France: Agence francaise de securite sanitaire des produits de sante (AFSSAPS)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Trastuzumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2016