Clinical trial NCT01007942: Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer
Official title: A Randomized Phase III, Double-blind, Placebo-controlled Multicenter Trial of Daily Everolimus in Combination With Trastuzumab and Vinorelbine, in Pretreated Women With HER2/Neu Over-expressing Locally Advanced or Metastatic Breast Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HER2/Neu Over-expressing Locally Advanced Breast Cancer
Metastatic Breast Cancer
Keywords: Metastatic breast cancer
locally advanced breast cancer
HER2/neu positive breast cancer
HER2/neu over-expressing
progressive-free survival (PFS)
over survival (OS)
bolero
bolero 3
Breast cancer
everolimus
HER+
vinorelbine
herceptin
trastuzumab
RAD001
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-11-04
Enrollment: 569
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progressive-free Survival (PFS) Per Investigator Assessment
timeFrame: Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Every 3 months until death up to 41 months
measure: Overall Response Rate (ORR)
timeFrame: Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Every 6 weeks until disease progression or death which ever occurred first up to about 41 months
measure: Median Time to Deterioration of the ECOG Performance Status Score
timeFrame: baseline, until disease progression or death up to about 41 months
measure: PRO: Time to Deterioration in Global Health Status/QoL Domain Score of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) (by at Least 10%)
timeFrame: Baseline, until disease progression or death up to about 41 months
measure: Everolimus Blood Concentrations by Leading Dose and Time Point
timeFrame: Cycle 2, Day 1
measure: Vinorelbine Blood Concentrations by Leading Dose and Time Point
timeFrame: Cycle 2, Day 1
measure: Trastuzumab Blood Concentrations by Leading Dose and Time Point
timeFrame: Cycle 3, Day 1
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona / Cancer Center AZ Onc Assoc
state: Arizona
city: Tucson
country: United States
facility: University of Arizona / Cancer Center Deptof Uof A/Arizona Cancer(3)
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego - Moores Cancer Center La Jolla - UCSD Moores Cancer
state: California
city: Greenwood Village
country: United States
facility: Rocky Mountain Cancer Centers RMCC
state: Colorado
city: Washington
country: United States
facility: Georgetown University/Lombardi Cancer Center Dept.of Lombardi CancerCtr (3)
state: District of Columbia
city: Boca Raton
country: United States
facility: Comprehensive Cancer Center - Boca Raton Deerfield Beach
state: Florida
city: Boca Raton
country: United States
facility: Comprehensive Cancer Center - Boca Raton Dept.of BocaRatonCompCanCtr
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists DeptofFloridaCancerSpecialists
state: Florida
city: Hollywood
country: United States
facility: Memorial Hospital Memorial Cancer Institute
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando(2)
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)
state: Georgia
city: Evanston
country: United States
facility: North Shore University Health System NSU
state: Illinois
city: Overland Park
country: United States
facility: Kansas City Cancer Center KCCC- South (2)
state: Kansas
city: Owning Mills
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: St. Louis Park
country: United States
facility: Park Nicollet Institute Dept. of Park Nicollet
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis University Cancer Center SLU Cancer Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center Unv Nebraska Med Ctr (2)
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Institute Dept. of Nevada Cancer (3)
state: Nevada
city: Summit
country: United States
facility: Overlook Hospital - Carol G Simon Cancer Center Carol G Simon
state: New Jersey
city: Lake Success
country: United States
facility: Clinical Research Alliance Dept.ofArenaOncologyAssoc(2)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center Dept. of DUMC (2)
state: North Carolina
city: Portland
country: United States
facility: Northwest Cancer Specialists Tutlatin
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute DeptofMageeWomen'sHospital(2)
state: Pennsylvania
city: Germantown
country: United States
facility: The Jones Clinic Dept .of The Jones Clinic (3)
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(6)
state: Tennessee
city: Dallas
country: United States
facility: Texas Cancer Center ( Medical City Dallas Hospital) Dept. of Texas Cancer Ctr. (2)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Presbyterian Hospital (2)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Onc - Amarillo
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Sammons
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Midtown
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center University of TX SW Med Ctr(2)
state: Texas
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center SC-5
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Baylor
state: Texas
city: Longview
country: United States
facility: Longview Cancer Center Longview Cancer Center (2)
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)
state: Texas
city: San Antonio
country: United States
facility: South Texas Oncology and Hematology, PA South Texas Oncology (2)
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center Dept.ofTylerCancerCtr. (2)
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Utah Cancer (2)
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists Fairfax No.VA (2)
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates Dept. of VOA (2)
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute Swedish Cancer Institute
state: Washington
city: Green Bay
country: United States
facility: Green Bay Oncology Green Bay Oncology
state: Wisconsin
city: C A B A
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Posadas
country: Argentina
facility: Novartis Investigative Site
state: Misiones
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Sante Fe
city: Rio Negro
country: Argentina
facility: Novartis Investigative Site
state: Viedma
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Kogarah
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: St. Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Southport
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Hobart
country: Australia
facility: Novartis Investigative Site
state: Tasmania
city: East Bentleigh
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Brussel
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Liège
country: Belgium
facility: Novartis Investigative Site
city: Namur
country: Belgium
facility: Novartis Investigative Site
city: Sint-Niklaas
country: Belgium
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Novy Jicin
country: Czech Republic
facility: Novartis Investigative Site
city: Olomouc
country: Czech Republic
facility: Novartis Investigative Site
city: Prague 5
country: Czech Republic
facility: Novartis Investigative Site
city: Bayonne
country: France
facility: Novartis Investigative Site
city: Besançon cedex
country: France
facility: Novartis Investigative Site
city: Hyères
country: France
facility: Novartis Investigative Site
city: La Chaussée St Victor
country: France
facility: Novartis Investigative Site
city: La Roche sur Yon Cedex
country: France
facility: Novartis Investigative Site
city: Nice Cedex 2
country: France
facility: Novartis Investigative Site
city: Saint-Brieuc Cédex
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Gerlingen
country: Germany
facility: Novartis Investigative Site
city: Halle/Saale
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Homburg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Minden
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Recklinghausen
country: Germany
facility: Novartis Investigative Site
city: Velbert
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Patra - RIO
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Heraklion Crete
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Gyor
country: Hungary
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Sondrio
country: Italy
facility: Novartis Investigative Site
state: SO
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Maebashi-city
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kumamoto City
country: Japan
facility: Novartis Investigative Site
state: Kumamoto
city: Kyoto-city
country: Japan
facility: Novartis Investigative Site
state: Kyoto
city: Suita-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Koto
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Fukuoka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Ciudad De Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: León
country: Mexico
facility: Novartis Investigative Site
state: Guanajuato
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Jaen
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: A Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Majadahonda
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz de Tenerife
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Songkla
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Fatih / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Truro
country: United Kingdom
facility: Novartis Investigative Site
state: Cornwall
city: Surrey
country: United Kingdom
facility: Novartis Investigative Site
state: England
city: Bournemouth
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.