Clinical trial NCT01142778: A Study of Bevacizumab Added to Trastuzumab Plus Docetaxel in the Neoadjuvant Setting in Participants With Early Stage HER2-Positive Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-06-11
Enrollment: 152
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Pathological Complete Response as per Chevallier's Classification as Reviewed by an Independent Committee
timeFrame: After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
Secondary outcomes:
measure: Percentage of Participants With Pathological Complete Response According to Chevallier's Classification as per Local Procedures
timeFrame: After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
measure: Percentage of Participants With Pathological Complete Response According to Sataloff's Classification as Reviewed by an Independent Committee
timeFrame: After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days)
measure: Percentage of Participants With Ultrasound Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Neodajuvant treatment period (21 weeks)
measure: Percentage of Participants With Conservative Surgery Post Neoadjuvant Treatment
timeFrame: Week 20 (between Day 28 and Day 35 after the Cycle 6, cycle length=21 days)
measure: Local Relapse-Free Interval (LRFI) According to Modified RECIST Criteria
timeFrame: From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
measure: Disease-Free Survival (DFS) According to Modified RECIST Criteria
timeFrame: From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
measure: Distant Disease-Free Interval (DDFI) According to Modified RECIST Criteria
timeFrame: From baseline to occurrence of relapse/disease or death of any cause (up to 5 years)
measure: Overall Survival
timeFrame: Baseline up to occurrence of death (up to 5 years)
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to 5 years
Other outcomes:
Locations:
city: Arras
country: France
facility: Centre Radiotherapie Marie Curie
city: Beauvais
country: France
facility: Centre Hospitalier; Hematologie-Oncologie
city: Bordeaux
country: France
facility: Clinique Tivoli; Sce Radiotherapie
city: Brest
country: France
facility: Hopital Augustin Morvan; Federation De Cancerologie
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin; Hopital De Jour
city: Clermont Ferrand
country: France
facility: Pole Sante Republique;Oncologie Hematologie
city: Dijon
country: France
facility: Centre Georges Francois Leclerc; Oncologie 3
city: Grenoble
country: France
facility: Institut Daniel Hollard
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental Les Oudairies
city: Limoges
country: France
facility: Hopital Dupuytren; Oncologie Medicale
city: Lyon
country: France
facility: Centre Leon Berard; Oncologie Genetique
city: Metz
country: France
facility: Hopital Clinique Claude Bernard; Oncologie Medicale
city: Montlucon
country: France
facility: Ch De Montlucon; Sce Med Interne Hemato Onco
city: Montpellier
country: France
facility: Institut régional du Cancer Montpellier
city: Nancy
country: France
facility: Centre D'Oncologie de Gentilly; Oncology
city: Nice
country: France
facility: Centre Antoine Lacassagne; Hopital De Jour A2
city: Paris
country: France
facility: Institut Curie; Oncologie Medicale
city: Paris
country: France
facility: GH Paris Saint Joseph; Hopital De Jour Oncologie
city: Paris
country: France
facility: HOPITAL TENON; Cancerologie Medicale
city: Perigueux
country: France
facility: Clinique Francheville; Radiotherapie
city: Reims CEDEX
country: France
facility: Institut Jean Godinot; Oncologie Medicale
city: Rennes
country: France
facility: Centre Eugene Marquis; Unite Huguenin
city: Saint Jean
country: France
facility: Clinique de L'Union; Oncologie
city: St Priest En Jarez
country: France
facility: Institut de Cancerologie de La Loire; Radiotherapie
city: Strasbourg
country: France
facility: Centre Paul Strauss; Oncologie Medicale
city: Toulouse
country: France
facility: Clinique Pasteur; Oncologie Medicale
city: Tours
country: France
facility: Centre Henry S Kaplan - CHU Bretonneau ; service oncologie
city: Vandoeuvre Les Nancy
country: France
facility: Centre Alexis Vautrin; Oncologie Medicale
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Coudert B, Pierga JY, Mouret-Reynier MA, Kerrou K, Ferrero JM, Petit T, Kerbrat P, Dupre PF, Bachelot T, Gabelle P, Giard S, Coeffic D, Bougnoux P, Prevost JB, Paintaud G, Thibault G, Hernandez J, Coudert M, Arnould L, Berriolo-Riedinger A. Use of [(18)F]-FDG PET to predict response to neoadjuvant trastuzumab and docetaxel in patients with HER2-positive breast cancer, and addition of bevacizumab to neoadjuvant trastuzumab and docetaxel in [(18)F]-FDG PET-predicted non-responders (AVATAXHER): an open-label, randomised phase 2 trial. Lancet Oncol. 2014 Dec;15(13):1493-1502. doi: 10.1016/S1470-2045(14)70475-9. Epub 2014 Oct 30.