Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT01007942

Last Updated: 2017-04-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

569 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-10-31

Study Completion Date

2015-06-30

Brief Summary

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This phase III, double-blind, placebo-controlled multinational study will assess the combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine and trastuzumab with respect to progressive-free survival and over survival in HER2/neu positive women with locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane.

Detailed Description

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Conditions

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HER2/Neu Over-expressing Locally Advanced Breast Cancer Metastatic Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Everolimus + vinorelbine + trastuzumab

Oral everolimus (5 mg/day) + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)

Group Type EXPERIMENTAL

everolimus

Intervention Type DRUG

Oral everolimus was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.

vinorelbine

Intervention Type DRUG

intravenous vinorelbine (25 mg/m2 weekly)

trastuzumab

Intervention Type DRUG

intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)

placebo + vinorelbine + trastuzumab

Oral daily matching placebo + intravenous vinorelbine (25 mg/m2 weekly) + intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Oral everolimus placebo was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.

vinorelbine

Intervention Type DRUG

intravenous vinorelbine (25 mg/m2 weekly)

trastuzumab

Intervention Type DRUG

intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)

Interventions

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everolimus

Oral everolimus was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.

Intervention Type DRUG

Placebo

Oral everolimus placebo was taken once 5 mg/day (2 × 2.5 mg tablets) and were packaged into blister packs.

Intervention Type DRUG

vinorelbine

intravenous vinorelbine (25 mg/m2 weekly)

Intervention Type DRUG

trastuzumab

intravenous trastuzumab (2 mg/kg weekly following a 4 mg/kg loading dose on Day 1 of Cycle 1 only)

Intervention Type DRUG

Other Intervention Names

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RAD001

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
* HER2+ status defined as IHC 3+ staining or in situ hybridization positive
* Patients with resistance to trastuzumab
* Prior taxane therapy
* Patients with an ECOG performance status of 0 - 2
* Patients with measurable disease as per RECIST criteria
* Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
* Patients must meet laboratory criteria defined in the study within 21 days prior to randomization

Exclusion Criteria

* Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
* More than three prior chemotherapy lines for advanced disease.
* Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed \>8 weeks prior to randomization
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
* Peripheral neuropathy ≥ grade 2 at randomization
* Active cardiac disease
* History of cardiac dysfunction
* Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
* Known hypersensitivity to any study medication
* Breastfeeding or 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 Arizona / Cancer Center AZ Onc Assoc

Tucson, Arizona, United States

Site Status

University of Arizona / Cancer Center Deptof Uof A/Arizona Cancer(3)

Tucson, Arizona, United States

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University of California San Diego - Moores Cancer Center La Jolla - UCSD Moores Cancer

La Jolla, California, United States

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Rocky Mountain Cancer Centers RMCC

Greenwood Village, Colorado, United States

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Georgetown University/Lombardi Cancer Center Dept.of Lombardi CancerCtr (3)

Washington D.C., District of Columbia, United States

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Comprehensive Cancer Center - Boca Raton Deerfield Beach

Boca Raton, Florida, United States

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Comprehensive Cancer Center - Boca Raton Dept.of BocaRatonCompCanCtr

Boca Raton, Florida, United States

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Florida Cancer Specialists DeptofFloridaCancerSpecialists

Fort Myers, Florida, United States

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Memorial Hospital Memorial Cancer Institute

Hollywood, Florida, United States

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MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando(2)

Orlando, Florida, United States

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Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)

Atlanta, Georgia, United States

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North Shore University Health System NSU

Evanston, Illinois, United States

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Kansas City Cancer Center KCCC- South (2)

Overland Park, Kansas, United States

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Maryland Oncology Hematology

Owning Mills, Maryland, United States

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Park Nicollet Institute Dept. of Park Nicollet

Saint Louis Park, Minnesota, United States

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St. Louis University Cancer Center SLU Cancer Center

St Louis, Missouri, United States

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

Omaha, Nebraska, United States

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Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)

Las Vegas, Nevada, United States

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Nevada Cancer Institute Dept. of Nevada Cancer (3)

Las Vegas, Nevada, United States

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Overlook Hospital - Carol G Simon Cancer Center Carol G Simon

Summit, New Jersey, United States

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Clinical Research Alliance Dept.ofArenaOncologyAssoc(2)

Lake Success, New York, United States

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Duke University Medical Center Dept. of DUMC (2)

Durham, North Carolina, United States

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Northwest Cancer Specialists Tutlatin

Portland, Oregon, United States

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University of Pittsburgh Cancer Institute DeptofMageeWomen'sHospital(2)

Pittsburgh, Pennsylvania, United States

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The Jones Clinic Dept .of The Jones Clinic (3)

Germantown, Tennessee, United States

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Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(6)

Nashville, Tennessee, United States

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Texas Cancer Center ( Medical City Dallas Hospital) Dept. of Texas Cancer Ctr. (2)

Dallas, Texas, United States

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Texas Oncology Presbyterian Hospital (2)

Dallas, Texas, United States

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Texas Oncology Texas Onc - Amarillo

Dallas, Texas, United States

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Texas Oncology Texas Oncology - Sammons

Dallas, Texas, United States

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Texas Oncology Midtown

Dallas, Texas, United States

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University of Texas Southwestern Medical Center University of TX SW Med Ctr(2)

Dallas, Texas, United States

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University of Texas/MD Anderson Cancer Center SC-5

Houston, Texas, United States

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Baylor College of Medicine Baylor

Houston, Texas, United States

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Longview Cancer Center Longview Cancer Center (2)

Longview, Texas, United States

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Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)

San Antonio, Texas, United States

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South Texas Oncology and Hematology, PA South Texas Oncology (2)

San Antonio, Texas, United States

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Tyler Cancer Center Dept.ofTylerCancerCtr. (2)

Tyler, Texas, United States

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Utah Cancer Specialists Utah Cancer (2)

Salt Lake City, Utah, United States

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Virginia Cancer Specialists Fairfax No.VA (2)

Fairfax, Virginia, United States

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Virginia Oncology Associates Dept. of VOA (2)

Norfolk, Virginia, United States

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Swedish Cancer Institute Swedish Cancer Institute

Seattle, Washington, United States

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Green Bay Oncology Green Bay Oncology

Green Bay, Wisconsin, United States

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Novartis Investigative Site

C A B A, Buenos Aires, Argentina

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Caba, Buenos Aires, Argentina

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Mar del Plata, Buenos Aires, Argentina

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Quilmes, Buenos Aires, Argentina

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Córdoba, Córdoba Province, Argentina

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Posadas, Misiones Province, Argentina

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Rosario, Sante Fe, Argentina

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San Miguel de Tucumán, Tucumán Province, Argentina

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Rio Negro, Viedma, Argentina

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Kogarah, New South Wales, Australia

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St Leonards, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Southport, Queensland, Australia

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Hobart, Tasmania, Australia

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East Bentleigh, Victoria, Australia

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Brussels, , Belgium

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Brussels, , Belgium

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Liège, , Belgium

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Namur, , Belgium

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Sint-Niklaas, , Belgium

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Shanghai, Shanghai Municipality, China

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Hangzhou, Zhejiang, China

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Nový Jičín, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Bayonne, , France

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Besançon, , France

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Hyères, , France

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La Chaussée-Saint-Victor, , France

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La Roche-sur-Yon, , France

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Nice, , France

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Saint-Brieuc Cédex, , France

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Villejuif, , France

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Mainz, Germany, Germany

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Berlin, , Germany

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Gerlingen, , Germany

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Halle, , Germany

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Homburg, , Germany

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Kiel, , Germany

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Minden, , Germany

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München, , Germany

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Recklinghausen, , Germany

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Velbert, , Germany

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Athens, Greece, Greece

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Heraklion Crete, Greece, Greece

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Athens, GR, Greece

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Patra - RIO, GR, Greece

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Thessaloniki, GR, Greece

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Thessaloniki, GR, Greece

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Győr, Hungary, Hungary

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Budapest, , Hungary

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Catania, CT, Italy

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Milan, MI, Italy

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Pavia, PV, Italy

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Sondrio, SO, 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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Maebashi, Gunma, Japan

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Sapporo, Hokkaido, Japan

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Yokohama, Kanagawa, Japan

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Kumamoto, Kumamoto, Japan

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Kyoto, Kyoto, Japan

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Osaka, Osaka, Japan

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Osaka, Osaka, Japan

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Suita, Osaka, Japan

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Bunkyo-ku, Tokyo, Japan

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Koto, Tokyo, Japan

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León, Guanajuato, Mexico

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Mexico City, Mexico City, Mexico

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Lublin, , Poland

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Warsaw, , Poland

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Singapore, Singapore, Singapore

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Bratislava, , Slovakia

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Košice, , Slovakia

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Córdoba, Andalusia, Spain

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Jaén, Andalusia, Spain

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Seville, Andalusia, Spain

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Barcelona, Barcelona, Spain

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Sabadell, Barcelona, Spain

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A Coruña, Galicia, Spain

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A Coruña, Galicia, Spain

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Madrid, Madrid, Spain

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Madrid, Madrid, Spain

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Majadahonda, Madrid, Spain

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San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain

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Valencia, Valencia, Spain

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Zaragoza, Zaragoza, Spain

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Bangkok, , Thailand

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Bangkok, , Thailand

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Songkhla, , Thailand

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Ankara, Turkey, Turkey (Türkiye)

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Izmir, Turkey, Turkey (Türkiye)

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Fatih / Istanbul, , Turkey (Türkiye)

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Truro, Cornwall, United Kingdom

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Surrey, England, United Kingdom

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Bournemouth, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Plymouth, , United Kingdom

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Countries

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United States Argentina Australia Belgium China Czechia France Germany Greece Hungary Israel Italy Japan Mexico Poland Singapore Slovakia Spain Thailand Turkey (Türkiye) United Kingdom

References

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Andre F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. doi: 10.1016/S1470-2045(14)70138-X. Epub 2014 Apr 14.

Reference Type DERIVED
PMID: 24742739 (View on PubMed)

Other Identifiers

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2008-008697-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001W2301

Identifier Type: -

Identifier Source: org_study_id

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