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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-013410-26 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Trastuzumab, Docetaxel, and Bevacizumab | Experimental | Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel along with bevacizumab in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the bevacizumab infusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment. |
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| Trastuzumab and Docetaxel | Active Comparator | Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of <70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment. |
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| Trastuzumab and Docetaxel (Standard Regimen) | Active Comparator | Participants will receive 2 cycles of trastuzumab and docetaxel once every 3 weeks. Then, participants with a response of >/=70% will receive trastuzumab and docetaxel in Cycles 3 to 6. All participants will receive trastuzumab alone in Cycle 7, and will undergo surgery after Cycle 7 and between 4 and 6 weeks after the study treatment perfusion in Cycle 6. After surgery, all participants will receive a further 11 cycles of trastuzumab plus radiotherapy with or without hormonal therapy as per site's standard practice, and will be followed for up to 5 years from start of neoadjuvant treatment. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bevacizumab | Drug | 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). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | |
| Percentage of Participants With Pathological Complete Response According to Sataloff's Classification as Reviewed by an Independent Committee |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Radiotherapie Marie Curie | Arras | 62000 | France | |||
| Centre Hospitalier; Hematologie-Oncologie |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25456368 | Derived | 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. |
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| Docetaxel | Drug | Docetaxel at a dose of 100 mg/m^2 will be administered as IV infusion from Cycles 1-6 (1 Cycle=21 days). |
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| Trastuzumab | Drug | 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). |
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| Surgery | Procedure | 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). |
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| Radiotherapy | Radiation | 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. |
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| Hormonal Therapy | Drug | 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. |
|
| After 6 cycles (18 weeks) of neoadjuvant therapy (cycle length=21 days) |
| Percentage of Participants With Ultrasound Response According to Modified Response Evaluation Criteria in Solid Tumors (RECIST) | Neodajuvant treatment period (21 weeks) |
| 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) |
| 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) |
| 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) |
| 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) |
| Overall Survival | Baseline up to occurrence of death (up to 5 years) |
| Percentage of Participants With Adverse Events | Baseline up to 5 years |
| Beauvais |
| 60021 |
| France |
| Clinique Tivoli; Sce Radiotherapie | Bordeaux | 33000 | France |
| Hopital Augustin Morvan; Federation De Cancerologie | Brest | 29200 | France |
| Centre Jean Perrin; Hopital De Jour | Clermont-Ferrand | 63011 | France |
| Pole Sante Republique;Oncologie Hematologie | Clermont-Ferrand | 63050 | France |
| Centre Georges Francois Leclerc; Oncologie 3 | Dijon | 21079 | France |
| Institut Daniel Hollard | Grenoble | 38000 | France |
| Centre Hospitalier Departemental Les Oudairies | La Roche-sur-Yon | 85925 | France |
| Hopital Dupuytren; Oncologie Medicale | Limoges | 87042 | France |
| Centre Leon Berard; Oncologie Genetique | Lyon | 69373 | France |
| Hopital Clinique Claude Bernard; Oncologie Medicale | Metz | 57000 | France |
| Ch De Montlucon; Sce Med Interne Hemato Onco | Montluçon | 03100 | France |
| Institut régional du Cancer Montpellier | Montpellier | 34298 | France |
| Centre D'Oncologie de Gentilly; Oncology | Nancy | 54100 | France |
| Centre Antoine Lacassagne; Hopital De Jour A2 | Nice | 06189 | France |
| Institut Curie; Oncologie Medicale | Paris | 75231 | France |
| GH Paris Saint Joseph; Hopital De Jour Oncologie | Paris | 75674 | France |
| HOPITAL TENON; Cancerologie Medicale | Paris | 75970 | France |
| Clinique Francheville; Radiotherapie | Périgueux | 24000 | France |
| Institut Jean Godinot; Oncologie Medicale | Reims | 51056 | France |
| Centre Eugene Marquis; Unite Huguenin | Rennes | 35042 | France |
| Clinique de L'Union; Oncologie | Saint-Jean | 31240 | France |
| Institut de Cancerologie de La Loire; Radiotherapie | Saint-Priest-en-Jarez | 42271 | France |
| Centre Paul Strauss; Oncologie Medicale | Strasbourg | 67065 | France |
| Clinique Pasteur; Oncologie Medicale | Toulouse | 31076 | France |
| Centre Henry S Kaplan - CHU Bretonneau ; service oncologie | Tours | 37044 | France |
| Centre Alexis Vautrin; Oncologie Medicale | Vandœuvre-lès-Nancy | 54511 | France |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D000077143 | Docetaxel |
| D000068878 | Trastuzumab |
| D013514 | Surgical Procedures, Operative |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D013812 | Therapeutics |
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