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Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT00876395

Last Updated: 2018-12-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

719 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-10

Study Completion Date

2017-10-23

Brief Summary

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The purpose of this Phase III study was to confirm the value of adding everolimus to weekly paclitaxel and trastuzumab as treatment of HER2-overexpressing metastatic breast cancer.

Detailed Description

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Conditions

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Breast Cancer

Keywords

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Breast Cancer HER2+ mTOR everolimus RAD001 first line metastatic locally advanced Trastuzumab Paclitaxel First Line Therapy HER2 Positive Metastatic Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Everolimus + Paclitaxel + Trastuzumab

Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

Everolimus was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

Trastuzumab

Intervention Type DRUG

Trastuzumab, 2 mg/kg weekly was used intravenously.

Paclitaxel

Intervention Type DRUG

Paclitaxel, 80 mg/m2 weekly was used intravenously.

Placebo + Paclitaxel + Trastuzumab

Placebo of everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Everolimus placebo was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

Trastuzumab

Intervention Type DRUG

Trastuzumab, 2 mg/kg weekly was used intravenously.

Paclitaxel

Intervention Type DRUG

Paclitaxel, 80 mg/m2 weekly was used intravenously.

Interventions

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Everolimus

Everolimus was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

Intervention Type DRUG

Placebo

Everolimus placebo was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

Intervention Type DRUG

Trastuzumab

Trastuzumab, 2 mg/kg weekly was used intravenously.

Intervention Type DRUG

Paclitaxel

Paclitaxel, 80 mg/m2 weekly was used intravenously.

Intervention Type DRUG

Other Intervention Names

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RAD001

Eligibility Criteria

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Inclusion Criteria

* Adult Women (≥ 18 years old).
* Histologically or cytologically confirmed invasive breast carcinoma with local recurrence or radiological evidence of metastatic disease.
* Must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease.
* HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
* Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment is allowed but should be discontinued \> 12 months prior to randomization.
* Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic settings) is allowed but should be discontinued at randomization. Patients treated with bisphosphonates at entry or who start bisphosphonates during study may continue this therapy during protocol treatment.
* Documentation of negative pregnancy test.
* Organ functions at time of inclusion.

Exclusion Criteria

* Prior mTOR inhibitors for the treatment of cancer.
* Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy.
* Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites, etc).
* Radiotherapy to ≥ 25% of the bone marrow within 4 weeks prior to randomization
* History of central nervous system metastasis.
* Impairment of gastrointestinal (GI) function or GI disease or active ulceration of the upper gastrointestinal tract.
* Serious peripheral neuropathy.
* Cardiac disease or dysfunction.
* Uncontrolled hypertension.
* HIV.
* Pregnant,
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.

Mobile, Alabama, United States

Site Status

Ironwood Cancer and Research Centers

Chandler, Arizona, United States

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Highlands Oncology Group

Fayetteville, Arkansas, United States

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Comprehensive Blood and Cancer Center Dept. of CBCC (2)

Bakersfield, California, United States

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St. Jude Heritage Medical Group Virginia Crosson Cancer Center

Fullerton, California, United States

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University of California at Los Angeles Dept. of UCLA

Los Angeles, California, United States

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Ventura County Hematology and Oncology

Oxnard, California, United States

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Cancer Care Associates Medical Group Dept. of CCA

Redondo Beach, California, United States

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Santa Barbara Hematolgy Oncology Medical Group Dept.ofSantaBarbaraHem/Onc

Santa Barbara, California, United States

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Central Coast Medical Oncology Corporation Onc Dept

Santa Maria, California, United States

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Rocky Mountain Cancer Centers RMCC - Denver-Midtown (3)

Greenwood Village, Colorado, United States

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Florida Cancer Specialists Dept.of FloridaCancerSpec. (2)

Fort Myers, Florida, United States

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Florida Cancer Specialists

West Palm Beach, Florida, United States

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Central Indiana Cancer Centers CICC - East (3)

Indianapolis, Indiana, United States

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Kansas City Cancer Center Dept. of KCCC

Overland Park, Kansas, United States

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University of Nebraska Medical Center Unv Nebraska Med Ctr (2)

Omaha, Nebraska, United States

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New York Oncology Hematology NYOH Amsterdam

Albany, New York, United States

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Beth Israel Medical Center Dept.ofBeth Israel Med. Ctr(2)

New York, New York, United States

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Northwest Cancer Specialists Vancouver Cancer Center (3)

Portland, Oregon, United States

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Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(5)

Nashville, Tennessee, United States

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Texas Oncology Charles A. Sammons Cancer Ctr

Dallas, Texas, United States

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Texas Oncology P A SC-Austin

Dallas, Texas, United States

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Tyler Cancer Center Dept.ofTylerCancerCtr. (2)

Tyler, Texas, United States

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Virginia Oncology Associates SC

Norfolk, Virginia, United States

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Virginia Cancer Institute VCI (3)

Richmond, Virginia, United States

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Novartis Investigative Site

CABA, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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Posadas, Misiones Province, Argentina

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Rosario, Sante Fe, Argentina

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Rio Negro, Viedma, Argentina

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Capital Federal, , Argentina

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Córdoba, , Argentina

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Southport, Queensland, Australia

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East Bentleigh, Victoria, Australia

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Charleroi, , Belgium

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Hasselt, , Belgium

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Verviers, , Belgium

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Wilrijk, , Belgium

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Yvoir, , Belgium

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Belo Horizonte, Minas Gerais, Brazil

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Belo Horizonte, Minas Gerais, Brazil

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Rio de Janeiro, Rio de Janeiro, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Saint-Jérôme, Quebec, Canada

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Guangzhou, Guangdong, China

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Harbin, Heilongjiang, China

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Nanjing, Jiangsu, China

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Nanjing, Jiangsu, China

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Shanghai, Shanghai Municipality, China

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Hangzhou, Zhejiang, China

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Beijing, , China

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Beijing, , China

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Guangzhou, , China

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Shanghai, , China

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Bogota, Cundinamarca, Colombia

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Bogotá, , Colombia

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Florida Blanca, , Colombia

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Montería, , Colombia

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Alexandria, , Egypt

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Cairo, , Egypt

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Limoges, , France

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Rouen, , France

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Saint-Herblain Cédex, , France

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Strasbourg, , France

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Thonon-les-Bains, , France

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Toulouse, , France

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Villejuif, , France

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Berlin, , Germany

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Chemnitz, , Germany

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Esslingen am Neckar, , Germany

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Kiel, , Germany

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Münster, , Germany

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Heraklion Crete, Greece, Greece

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Athens, GR, Greece

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Thessaloniki, GR, Greece

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Athens, , Greece

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Athens, , Greece

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Shatin, New Territories, Hong Kong, Hong Kong

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Hong Kong SAR, , Hong Kong

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Tuenmen, , Hong Kong

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Wilton, Cork, Ireland

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Dublin, , Ireland

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Monza, MB, Italy

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Modena, MO, Italy

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Camposampiero, PD, Italy

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Roma, RM, Italy

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Napoli, , Italy

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Nagoya, Aichi-ken, Japan

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Kashiwa, Chiba, Japan

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Fukuoka, Fukuoka, Japan

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Kitakyushu, Fukuoka, Japan

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Maebashi, Gunma, Japan

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Sapporo, Hokkaido, Japan

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Isehara, Kanagawa, Japan

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Kumamoto, Kumamoto, Japan

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Sakyo-ku, Kyoto, Japan

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Osaka, Osaka, Japan

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Suita, Osaka, Japan

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Kitaadachi-gun, Saitama, Japan

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Bunkyo-ku, Tokyo, Japan

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Chuo-ku, Tokyo, Japan

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Osaka, , Japan

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Beirut, , Lebanon

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El Achrafiyé, , Lebanon

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Mexico City, Mexico City, Mexico

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Zaragoza, Veracruz, Mexico

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San Borja, Lima region, Peru

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Surquillo, Lima region, Peru

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San Juan VA Hospital San Juan Hospital

San Juan, , Puerto Rico

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Kazan', Tatarstan Republic, Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Bloemfontein, , South Africa

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Durban, , South Africa

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Pretoria, , South Africa

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Gyeonggi-do, Korea, South Korea

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Seoul, Korea, South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Geneva, , Switzerland

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Zurich, , Switzerland

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Taipei, Taiwan, ROC, Taiwan

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Kaohsiung City, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Altunizade, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Truro, Cornwall, United Kingdom

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London, , United Kingdom

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Sutton, , United Kingdom

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Valencia, Carabobo, Venezuela

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Countries

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Hungary Poland United States Argentina Australia Belgium Brazil Canada China Colombia Egypt France Germany Greece Hong Kong Ireland Italy Japan Lebanon Mexico Peru Puerto Rico Russia South Africa South Korea Switzerland Taiwan Turkey (Türkiye) United Kingdom Venezuela

References

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Toi M, Shao Z, Hurvitz S, Tseng LM, Zhang Q, Shen K, Liu D, Feng J, Xu B, Wang X, Lee KS, Ng TY, Ridolfi A, Noel-Baron F, Ringeisen F, Jiang Z. Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1. Breast Cancer Res. 2017 Apr 11;19(1):47. doi: 10.1186/s13058-017-0839-0.

Reference Type DERIVED
PMID: 28399902 (View on PubMed)

Buyse M, Hurvitz SA, Andre F, Jiang Z, Burris HA, Toi M, Eiermann W, Lindsay MA, Slamon D. Statistical controversies in clinical research: statistical significance-too much of a good thing .... Ann Oncol. 2016 May;27(5):760-2. doi: 10.1093/annonc/mdw047. Epub 2016 Feb 9.

Reference Type DERIVED
PMID: 26861602 (View on PubMed)

Hurvitz SA, Andre F, Jiang Z, Shao Z, Mano MS, Neciosup SP, Tseng LM, Zhang Q, Shen K, Liu D, Dreosti LM, Burris HA, Toi M, Buyse ME, Cabaribere D, Lindsay MA, Rao S, Pacaud LB, Taran T, Slamon D. Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial. Lancet Oncol. 2015 Jul;16(7):816-29. doi: 10.1016/S1470-2045(15)00051-0. Epub 2015 Jun 16.

Reference Type DERIVED
PMID: 26092818 (View on PubMed)

Other Identifiers

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2008-006556-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001J2301

Identifier Type: -

Identifier Source: org_study_id