NCT01783444

Brief Summary

This was a three-arm, randomized, open label, multi-center phase II study investigating the combination of everolimus (10mg daily) with exemestane (25mg daily) versus everolimus (10mg daily) versus capecitabine (1250mg/m2 twice daily for 14 days, 3-week cycle) in patients with estrogen-receptor positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
309

participants targeted

Target at P75+ for phase_2 breast-cancer

Timeline
Completed

Started Feb 2013

Typical duration for phase_2 breast-cancer

Geographic Reach
18 countries

83 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 11, 2013

Completed
25 days until next milestone

First Posted

Study publicly available on registry

February 5, 2013

Completed
21 days until next milestone

Study Start

First participant enrolled

February 26, 2013

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 2, 2018

Completed
28 days until next milestone

Study Completion

Last participant's last visit for all outcomes

July 30, 2018

Completed
2.6 years until next milestone

Results Posted

Study results publicly available

February 26, 2021

Completed
Last Updated

February 26, 2021

Status Verified

February 1, 2021

Enrollment Period

5.3 years

First QC Date

January 11, 2013

Results QC Date

April 29, 2019

Last Update Submit

February 19, 2021

Conditions

Keywords

EverolimusExemestaneCapecitabinelocally advancedmetastaticbreast cancerbreast cancer positive for human epidermal growth factor receptor 2HER2HER2 positivebreast cancer progressionestrogen-receptor positive breast cancerER

Outcome Measures

Primary Outcomes (1)

  • Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Everolimus Alone

    Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not have an event, PFS was censored at the date of the last adequate tumor assessment. PFS was compared between the everolimus + exemestane combination therapy with the everolimus monotherapy.

    Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 39 months

Secondary Outcomes (7)

  • Progression Free Survival (PFS) - Everolimus Plus Exemestane Versus Capecitabine Alone

    Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 39 months

  • Overall Survival (OS)

    Every 3 months following end of treatment visit, assessed for approximately 54 months

  • Overall Response Rate (ORR)

    From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months

  • Clinical Benefit Rate (CBR)

    From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 43 months

  • Time to Eastern Cooperative Oncology Group (ECOG) Performance Deterioration

    Baseline, every 6 weeks up to about 43 months

  • +2 more secondary outcomes

Study Arms (3)

Capecitabine 1250 mg/m2

EXPERIMENTAL

Capecitabine (1250 mg/m2 twice daily) for two weeks, followed by one week rest period in 3-weeks cycles (investigational arm).

Drug: Capecitabine

Everolimus 10 mg

EXPERIMENTAL

Everolimus (10 mg daily) (investigational arm).

Drug: Everolimus

Everolimus 10 mg + Exemestane 25 mg

ACTIVE COMPARATOR

Everolimus (10 mg daily) with Exemestane (25 mg daily) (control arm).

Drug: ExemestaneDrug: Everolimus

Interventions

Capecitabine, tablets for oral use, 1250 mg/m² twice daily for 2 weeks followed by one week rest (3-week-cycle) (locally supplied)

Also known as: Capecitabine monotherapy
Capecitabine 1250 mg/m2

Exemestane, tablets for oral use, 25 mg per day in (locally supplied)

Also known as: Control arm
Everolimus 10 mg + Exemestane 25 mg

Everolimus, 5 mg tablets for oral use, 10 mg (2 x 5 mg) per day (centrally supplied)

Also known as: Everolimus monotherapy, RAD001
Everolimus 10 mgEverolimus 10 mg + Exemestane 25 mg

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \- Women with locally advanced, recurrent, or metastatic breast cancer along with confirmation of estrogen-receptor positive (ER+). Measurable disease defined as at least one lesion ≥ 10 mm by CT or MRI that can be accurately measured in at least one dimension (CT scan slice thickness ≤ 5 mm) OR • Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above.

You may not qualify if:

  • \- Patients who received more than one chemotherapy line. Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis.Previous treatment with exemestane, mTOR inhibitors, PI3K inhibitors or AKT inhibitors.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (83)

University of California at Los Angeles Mattel Children's Hospital

Los Angeles, California, 90095, United States

Location

Sharp Memorial Hospital SharpClinicalOncologyResearch

San Diego, California, 92123, United States

Location

Florida Cancer Specialists Dept of Oncology (2)

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists FL Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Lahey Clinic Dept of Lahey Clinic (2)

Burlington, Massachusetts, 01805, United States

Location

New England Hematology/ Oncology Associates, P.C. SC

Newton, Massachusetts, 02462, United States

Location

Glacier View Research Institute - Cancer SC

Kalispell, Montana, 59901, United States

Location

Trinitas Comprehensive Cancer Center SC

Elizabeth, New Jersey, 07207, United States

Location

Hackensack University Medical Center Dept of Oncology

Hackensack, New Jersey, 07601, United States

Location

Rutgers-New Jersey Medical School SC

Newark, New Jersey, 07101, United States

Location

Oncology Hematology Care Inc Oncology Hematology Care 2

Cincinnati, Ohio, 45242, United States

Location

Oklahoma Cancer Specialists and Research Institute Oklahoma Cancer Specialists

Tulsa, Oklahoma, 74136, United States

Location

Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology

Chattanooga, Tennessee, 37404, United States

Location

The Jones Clinic SC

Germantown, Tennessee, 38138, United States

Location

University of Tennessee SC

Knoxville, Tennessee, 27920-6969, United States

Location

Sarah Cannon Research Institute SC (2)

Nashville, Tennessee, 37203, United States

Location

The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD

Fort Worth, Texas, 76104, United States

Location

University of Virginia Health Systems SC-4

Charlottesville, Virginia, 22908-0334, United States

Location

Northwest Medical Specialties Dept of Onc

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1025ABI, Argentina

Location

Novartis Investigative Site

Posadas, Misiones Province, Argentina

Location

Novartis Investigative Site

Rosario, Santa Fe Province, S2000KZE, Argentina

Location

Novartis Investigative Site

Rio Negro, Viedma, 8500, Argentina

Location

Novartis Investigative Site

Córdoba, X5016KEH, Argentina

Location

Novartis Investigative Site

Randwick, New South Wales, 2031, Australia

Location

Novartis Investigative Site

Wahroonga, New South Wales, 2076, Australia

Location

Novartis Investigative Site

Malvern, Victoria, 3144, Australia

Location

Novartis Investigative Site

Parkville, Victoria, 3050, Australia

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Novartis Investigative Site

Natal, Rio Grande do Norte, 59075 740, Brazil

Location

Novartis Investigative Site

Passo Fundo, Rio Grande do Sul, 99010-260, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01317-002, Brazil

Location

Novartis Investigative Site

Aarhus, 8000 C, Denmark

Location

Novartis Investigative Site

Copenhagen, DK-2100, Denmark

Location

Novartis Investigative Site

Næstved, DK-4700, Denmark

Location

Novartis Investigative Site

Odense C, DK 5000, Denmark

Location

Novartis Investigative Site

Roskilde, 4000, Denmark

Location

Novartis Investigative Site

Vejle, 7100, Denmark

Location

Novartis Investigative Site

Budapest, HUN, 1145, Hungary

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Tatabánya, 2800, Hungary

Location

Novartis Investigative Site

Hyderabad, Andhra Pradesh, 500 034, India

Location

Novartis Investigative Site

Pune, Maharashtra, 411013, India

Location

Novartis Investigative Site

Kolkata, West Bengal, 700 053, India

Location

Novartis Investigative Site

Mumbai, 400 012, India

Location

Novartis Investigative Site

Limerick, Co Limerick, Ireland

Location

Novartis Investigative Site

Dublin, D04 T6F, Ireland

Location

Novartis Investigative Site

Galway, Ireland

Location

Novartis Investigative Site

Beirut, 1107 2020, Lebanon

Location

Novartis Investigative Site

Beirut, Lebanon

Location

Novartis Investigative Site

El Achrafiyé, 166830, Lebanon

Location

Novartis Investigative Site

Hazmiyeh, 470, Lebanon

Location

Novartis Investigative Site

Saida, 652, Lebanon

Location

Novartis Investigative Site

Kota Kinabalu, Sabah, 88586, Malaysia

Location

Novartis Investigative Site

Kuala Lumpur, 59100, Malaysia

Location

Novartis Investigative Site

Jesus Maria, Lima region, 11, Peru

Location

Novartis Investigative Site

San Borja, Lima region, 41, Peru

Location

Novartis Investigative Site

Surquillo, Lima region, 34, Peru

Location

Novartis Investigative Site

Arequipa, Peru

Location

Novartis Investigative Site

Arkhangelsk, 163045, Russia

Location

Novartis Investigative Site

Moscow, 115478, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197758, Russia

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28033, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Eskilstuna, SE-631 88, Sweden

Location

Novartis Investigative Site

Jönköping, 551 85, Sweden

Location

Novartis Investigative Site

Stockholm, SE-171 76, Sweden

Location

Novartis Investigative Site

Uppsala, SE-751 85, Sweden

Location

Novartis Investigative Site

Vaxjo, SE-351 85, Sweden

Location

Novartis Investigative Site

Västerås, 721 89, Sweden

Location

Novartis Investigative Site

Lopburi, Changwat Lop Buri, 15000, Thailand

Location

Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

Location

Novartis Investigative Site

Muang, 40002, Thailand

Location

Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34303, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35340, Turkey (Türkiye)

Location

Novartis Investigative Site

East Kilbride, G75 8RG, United Kingdom

Location

Novartis Investigative Site

Middlesbrough, TS4 3BW, United Kingdom

Location

Novartis Investigative Site

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

  • Jerusalem G, de Boer RH, Hurvitz S, Yardley DA, Kovalenko E, Ejlertsen B, Blau S, Ozguroglu M, Landherr L, Ewertz M, Taran T, Fan J, Noel-Baron F, Louveau AL, Burris H. Everolimus Plus Exemestane vs Everolimus or Capecitabine Monotherapy for Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer: The BOLERO-6 Randomized Clinical Trial. JAMA Oncol. 2018 Oct 1;4(10):1367-1374. doi: 10.1001/jamaoncol.2018.2262.

MeSH Terms

Conditions

Breast NeoplasmsNeoplasm Metastasis

Interventions

CapecitabineexemestaneEverolimus

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesSirolimusMacrolidesLactonesOrganic Chemicals

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 11, 2013

First Posted

February 5, 2013

Study Start

February 26, 2013

Primary Completion

July 2, 2018

Study Completion

July 30, 2018

Last Updated

February 26, 2021

Results First Posted

February 26, 2021

Record last verified: 2021-02

Data Sharing

IPD Sharing
Will share

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

More information

Locations