A Study of Bevacizumab Added to Trastuzumab Plus Docetaxel in the Neoadjuvant Setting in Participants With Early Stage HER2-Positive Breast Cancer

Breast Cancer Clinical Trial

— AVATAXHER  

Official title:

An Open-Label, Randomized, Multicenter, Phase II, Non Comparative, Exploratory Study on Neoadjuvant Treatment With Trastuzumab Plus Docetaxel Plus Bevacizumab According to Positon Emission Tomography (PET) Value Modification in Patients With Early Stage HER2 Positive Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01142778
• Other study ID #: ML22229
• Secondary ID: 2009-013410-26
• Status: Completed
• Phase: Phase 2
• First received: June 10, 2010
• Last updated: March 15, 2018
• Start date: May 19, 2010
• Est. completion date: December 13, 2017

Study information

• Verified date: March 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized study will assess the effect of adding bevacizumab to trastuzumab plus docetaxel in neoadjuvant therapy in participants with early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. After 2 cycles of trastuzumab and docetaxel once every 3 weeks, participants with a response (change in standard uptake value [SUV]) of less than (<) 70 percent (%) on Positron Emission Tomography (PET) will be randomized in a 2:1 ratio to receive Cycles 3 to 6 of trastuzumab (6 milligrams per kilogram [mg/kg]) and docetaxel (100 milligrams per square meter [mg/m^2]) with or without bevacizumab (15 mg/kg). Participants with a response of greater than or equal to (>/=) 70% will receive trastuzumab plus docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery (as per investigator's discretion) after Cycle 7 and between 4 and 6 weeks after the treatment perfusion of Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy (starting from 4-8 weeks after surgery during 4-6 weeks, according to site's standard practice) with or without hormonal therapy (mandatory if positive hormone receptors). Participants will be followed for up to 5 years from start of neoadjuvant treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: December 13, 2017
• Est. primary completion date: December 13, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants with early stage HER2-positive breast cancer

• Scheduled to receive neoadjuvant therapy with the objective of conservative surgery

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

• Participants with partial or total lobular carcinoma

• Participants with inflammatory breast cancer

• Previous treatment with chemotherapy, radiation therapy or hormonal therapy for breast cancer

• Previous history of cancer (other than curatively treated basal and squamous cell carcinoma of the skin and/or in situ carcinoma of the cervix) relapsing within the 5 years before study entry or in situ contralateral breast carcinoma

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Bevacizumab
Bevacizumab at a dose of 15 mg/kg will be administered as IV infusion over 90 minutes from Cycles 3-6 (1 Cycle=21 days).
• Docetaxel
Docetaxel at a dose of 100 mg/m^2 will be administered as IV infusion from Cycles 1-6 (1 Cycle=21 days).
• Trastuzumab
Trastuzumab will be administered as a loading dose of 8 mg/kg as IV infusion in Cycle 1, followed by subsequent dose of 6 mg/kg as IV infusion in Cycles 2 to 7, and during additional 11 cycles post surgery (1 Cycle=21 days).

Procedure:
• Surgery
All participants will undergo surgery (as per investigator's discretion) after Cycle 7 and between 4 and 6 weeks after the study treatment infusion in Cycle 6 (1 Cycle=21 days).

Radiation:
• Radiotherapy
All participants will receive radiotherapy starting about 4 to 8 weeks after surgery, and will last around 4 to 6 weeks as per site's standard practice.

Drug:
• Hormonal Therapy
Participants who are hormone receptors positive, will receive hormonal therapy after completion of radio therapy period as per investigator's discretion and site's standard practice.

Locations

Country	Name	City	State
France	Centre Radiotherapie Marie Curie	Arras
France	Centre Hospitalier; Hematologie-Oncologie	Beauvais
France	Clinique Tivoli; Sce Radiotherapie	Bordeaux
France	Hopital Augustin Morvan; Federation De Cancerologie	Brest
France	Centre Jean Perrin; Hopital De Jour	Clermont Ferrand
France	Pole Sante Republique;Oncologie Hematologie	Clermont Ferrand
France	Centre Georges Francois Leclerc; Oncologie 3	Dijon
France	Institut Daniel Hollard	Grenoble
France	Centre Hospitalier Departemental Les Oudairies	La Roche Sur Yon
France	Hopital Dupuytren; Oncologie Medicale	Limoges
France	Centre Leon Berard; Oncologie Genetique	Lyon
France	Hopital Clinique Claude Bernard; Oncologie Medicale	Metz
France	Ch De Montlucon; Sce Med Interne Hemato Onco	Montlucon
France	Institut régional du Cancer Montpellier	Montpellier
France	Centre D'Oncologie de Gentilly; Oncology	Nancy
France	Centre Antoine Lacassagne; Hopital De Jour A2	Nice
France	GH Paris Saint Joseph; Hopital De Jour Oncologie	Paris
France	HOPITAL TENON; Cancerologie Medicale	Paris
France	Institut Curie; Oncologie Medicale	Paris
France	Clinique Francheville; Radiotherapie	Perigueux
France	Institut Jean Godinot; Oncologie Medicale	Reims CEDEX
France	Centre Eugene Marquis; Unite Huguenin	Rennes
France	Clinique de L'Union; Oncologie	Saint Jean
France	Institut de Cancerologie de La Loire; Radiotherapie	St Priest En Jarez
France	Centre Paul Strauss; Oncologie Medicale	Strasbourg
France	Clinique Pasteur; Oncologie Medicale	Toulouse
France	Centre Henry S Kaplan - CHU Bretonneau ; service oncologie	Tours
France	Centre Alexis Vautrin; Oncologie Medicale	Vandoeuvre Les Nancy

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 Pathological Complete Response as per Chevallier's Classification as Reviewed by an Independent Committee		After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
Secondary	Percentage of Participants With Pathological Complete Response According to Chevallier's Classification as per Local Procedures		After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
Secondary	Percentage of Participants With Pathological Complete Response According to Sataloff's Classification as Reviewed by an Independent Committee		After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
Secondary	Percentage of Participants With Ultrasound Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)		Neodajuvant treatment period (21 weeks)
Secondary	Percentage of Participants With Conservative Surgery Post Neoadjuvant Treatment		Week 20 (between Day 28 and Day 35 after the Cycle 6, cycle length=21 days)
Secondary	Local Relapse-Free Interval (LRFI) According to Modified RECIST Criteria		From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
Secondary	Disease-Free Survival (DFS) According to Modified RECIST Criteria		From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
Secondary	Distant Disease-Free Interval (DDFI) According to Modified RECIST Criteria		From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
Secondary	Overall Survival		Baseline up to occurrence of death (up to 5 years)
Secondary	Percentage of Participants With Adverse Events		Baseline up to 5 years