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A Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in Advance Breast Cancer. (BOLERO-6)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01783444
First received: January 11, 2013
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

This study will assess the efficacy and tolerability of everolimus and capecitabine monotherapies compared to everolimus/exemestane combination in woman with ER + advanced breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Capecitabine
Drug: Exemestane
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in the Treatment of Postmenopausal Women With ER+Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Prior Letrozole or Anastrozole.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 28 months after first patient randomized or once 150 PFS have occurred ] [ Designated as safety issue: No ]
    Once 150 PFS events have occured (determined by local assessment). To estimate the hazard ratio of PFS for everolimus plus exemestane versus everolimus alone in postmenopausal women with ER positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Every 3 months following the end of study visit until 2015 (up to 3 years) ] [ Designated as safety issue: No ]
    To evaluate the treatment groups with respect to Overall Survival. End of study visit is defined as time when progression of disease recorded or death whichever comes first.

  • Overall response rate [ Time Frame: From the date of first dose of study medication until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately for 28 months ] [ Designated as safety issue: No ]
    Overall response rate (ORR) based on the local radiologist/investigator's tumor assessment (RECIST 1.1)

  • Clinical benefit rate (CBR) [ Time Frame: From the date of first dose of study medication until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 28 months ] [ Designated as safety issue: No ]
    Clinical Benefit Rate is defined as the proportion of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD) with duration of 24 weeks or longer.

  • Changes in ECOG (Eastern Cooperative Oncology Group) performance status [ Time Frame: Baseline, Day 1, every 6 weeks for approximately 8 months ] [ Designated as safety issue: No ]
    The ECOG performance status scale (1-5) allows patients to be classified as to their functional impairment, ECOG performance status will be compared to baseline ECOG performance classification.

  • Change in quality of life scores over time: EORTC (QLQ-C30)/EORTC module (BR23) [ Time Frame: Baseline, every 6 weeks for approximately 8 months ] [ Designated as safety issue: No ]
  • Time to quality of life (QoL)deterioration : TSQM score [ Time Frame: Baseline, week 3,6, 12 for approximately 8 months ] [ Designated as safety issue: No ]
  • Safety: Incidence of Adverse Event(s) [ Time Frame: every study visit for approximately 8 months ] [ Designated as safety issue: Yes ]
  • Safety: Incidence of Serious Adverse Events [ Time Frame: every study visit for approximately 8 months ] [ Designated as safety issue: Yes ]
  • Safety: changes in vital signs when compared to baseline vital signs [ Time Frame: baseline, every study visit for approximately 8 months ] [ Designated as safety issue: Yes ]
  • Safety: changes in laboratory values compared to laboratory values obtained at the baseline visit [ Time Frame: baseline, every study visit for approximately 8 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: February 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Capecitabine Monotherapy
100 patients will be randomized to the Capecitabine monotherapy arm (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest period in 3-weeks cycles.
Drug: Capecitabine
Capecitabine, for oral use 1250 mg/m2 twice daily for 2 weeks followed by one week rest (3-week cycle). Capecitabine will be locally supplied by the Investigator.
Other Name: Capecitabine monotherapy
Experimental: Everolimus Monotherapy
100 patients will be randomized to this arm and will received Everolimus (10mg daily).
Drug: Everolimus
Everolimus will be centrally dispensed via IWRS. Everolimus will be taken as oral tablets for oral use 10 mg (2 × 5 mg) daily.
Other Name: RAD001
Active Comparator: Everolimus with Exemestane
100 patients will be randomized to the control arm of this study, everolimus (10mg daily) with exemestane (25mg daily).
Drug: Exemestane
Exemestane tablets of 25 mg will be taken orally once per day. Dose modifications in the management of adverse events is allowed.
Other Name: Control Arm

Detailed Description:

This is 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. The reference therapy (control arm) used in the course of this trial is the combination arm of everolimus plus exemestane. The investigational therapies in the context of this study are everolimus monotherapy and capecitabine monotherapy. All treatments will be taken orally until disease progression, intolerable toxicity or withdrawal of patient's informed consent. Patients will be randomly assigned with equal allocation to one of the treatment arms:

  1. Exemestane (25mg daily) in combination with everolimus (10mg daily)
  2. Everolimus (10mg daily)
  3. Capecitabine (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest period in 3-weeks cycles.

Treatment assignment will be stratified by the presence of visceral disease (yes vs. no). Visceral refers to lung, liver, heart, ovary, spleen, kidney, adrenal gland, malignant pleural or pericardial effusion or malignant ascites.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

-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

Exclusion Criteria:

-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

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01783444

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Hide Study Locations
Locations
United States, California
Long Beach Memorial Medical Care SC Recruiting
Long Beach, California, United States, 90806
Contact: Deborah Fridman       dfridman@memorialcare.org   
Principal Investigator: Bichlien Nguyen         
University of California at Los Angeles Mattel Children's Hospital Recruiting
Los Angeles, California, United States, 90095
Contact: Vanity Campbell       vancampbell@mednet.ucla.edu   
Principal Investigator: Sara A. Hurvitz         
University of California - Davis SC Recruiting
Sacramento, California, United States, 95817
Contact: Patricia Tuohy    916-734-8134    patricia.tuohy@ucdmc.ucdavis.edu   
Principal Investigator: Helen K. Chew         
Sharp Memorial Hospital SharpClinicalOncologyResearch Recruiting
San Diego, California, United States, 92123
Contact: Matthew Geriak    858-939-5062    Matthew.geriak@sharp.com   
Principal Investigator: Rajesh Belani         
United States, Florida
Florida Cancer Specialists Dept of Onc Recruiting
Fort Myers, Florida, United States, 33901
Contact: BJ Conklin    727-216-1143    bconklin@flcancer.com   
Principal Investigator: Robert W. Weaver         
Florida Cancer Specialists Dept of Oncology Recruiting
Fort Myers, Florida, United States, 33901
Contact: Julie Trundle       Julie.Trundle@scresearch.net   
Principal Investigator: Lowell L. Hart         
United States, Idaho
St. Lukes Hospital Mountain State Tumor Institute Dept of Oncology Withdrawn
Boise, Idaho, United States, 83712
United States, Kansas
Stormont Vail Healthcare - Cotton-O'Neil Clinic Dept of Oncology Recruiting
Topeka, Kansas, United States, 66606
Contact: Scott Harrison    785-354-5300    saharris@stormontvail.org   
Principal Investigator: Mehmood E Hashmi         
United States, Louisiana
Crescent City Research Consortium, LLC SC-3 Recruiting
Metairie, Louisiana, United States, 70006
Contact: Vivian Davis    504-454-5368    vdavis@wjmc.org   
Principal Investigator: Thomas Cosgriff         
United States, Maine
Eastern Maine Medical Center Research Center SC Not yet recruiting
Bangor, Maine, United States, 04401
Contact: Teresa White    207-973-4249    twhite@emhs.org   
Principal Investigator: Thomas H. Openshaw         
United States, Maryland
Carroll Regional Cancer Center Recruiting
Westminster, Maryland, United States, 21157
Contact: Corilynn Hughes    410-871-6400    corilynn.hughes@usoncology.com   
Principal Investigator: Flavio Kruter         
United States, Massachusetts
Beth Israel Deaconess Medical Center Dept of Oncology Recruiting
Boston, Massachusetts, United States, 02215
Contact: Heena P. Patel    617-667-3347    hpatel@bidmc.harvard.edu   
Principal Investigator: Steven Come         
Lahey Clinic Dept of Lahey Clinic (2) Recruiting
Burlington, Massachusetts, United States, 01805
Contact: Kori Hesse    781-744-7487    Kori.hesse@lahey.org   
Principal Investigator: Corrine Zarwan         
New England Hematology/ Oncology Associates, P.C. SC Recruiting
Newton, Massachusetts, United States, 02462
Contact: Elizabeth Strand    617-243-5619      
Principal Investigator: Caroline Block         
United States, Michigan
MidMichigan Medical Center- Midland SC Not yet recruiting
Midland, Michigan, United States, 48670
Contact: Sandra Moore       sandra.moore@midmichigan.org   
Principal Investigator: Michel Hurtubise         
United States, Montana
Glacier View Research Institute - Cancer SC Recruiting
Kalispell, Montana, United States, 59901
Contact: Magen Lefkowicz    406-752-8900 ext 231    mlefkowicz@krmc.org   
Principal Investigator: Karen Hunt         
United States, New Jersey
Trinitas Comprehensive Cancer Center SC Recruiting
Elizabeth, New Jersey, United States, 07207
Contact: John Mikros    908-994-8539    jmikros@trinitas.org   
Principal Investigator: Gerardo Capo         
Hackensack University Medical Center Dept of Oncology Recruiting
Hackensack, New Jersey, United States, 07601
Contact: William Marrero    551-996-5098    wmarrero@hackensackumc.org   
Principal Investigator: Stanley Waintraub         
Rutgers-New Jersey Medical School SC Recruiting
Newark, New Jersey, United States, 07101
Contact: Karen Jackson    973-972-5034    jacksoka@umdnj.edu   
Principal Investigator: Shail Maingi         
United States, New York
Richmond University Medical Center SC Recruiting
Staten Island, New York, United States, 10310
Contact: Angela Gilbride    718-818-1025    mSmith3@rumcsi.org   
Principal Investigator: Thomas Forlenza         
United States, Ohio
Oncology/Hematology Care, Inc. SC Recruiting
Cincinnati, Ohio, United States, 45242
Contact: Sara M Gonce    513-751-2273    sgonce@ohcare.com   
Principal Investigator: Patrick Ward         
United States, Oklahoma
Tulsa Cancer Institute Recruiting
Tulsa, Oklahoma, United States, 74136
Contact: Brenda K Osbourne    918-292-8085    Brenda.Osbourne@cancercareokla.com   
Principal Investigator: Kevin Weibel         
United States, Tennessee
Chattanooga Oncology and Hematology Assoicates, PC SC Recruiting
Chattanooga, Tennessee, United States, 37404
Contact: Bobby Stillman    +1 423 698 1844    bstillman@tnonc.com   
Principal Investigator: Brooke Ratliff Daniel         
The Jones Clinic SC Recruiting
Germantown, Tennessee, United States, 38138
Contact: Lori Lynch    901-685-5969 ext 328    llynch@jonescancerclinic.com   
Principal Investigator: Clyde M. Jones         
University of Tennessee SC Recruiting
Knoxville, Tennessee, United States, 27920-6969
Contact: David Cornelius    865-305-9773 ext 4    dcorneli@utmck.edu   
Principal Investigator: Timothy J Panella         
Sarah Cannon Research Institute SC (2) Recruiting
Nashville, Tennessee, United States, 37203
Contact: Julie Trundle    615-329-7497    Julie.Trundle@scresearch.net   
Principal Investigator: Denise A. Yardley         
United States, Texas
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD Recruiting
Fort Worth, Texas, United States, 76104
Contact: Melissa M Bagwell    +1 817 759 7023    mbagwell@txcc.com   
Principal Investigator: Robyn Ruble Young         
United States, Virginia
University of Virginia Health Systems SC-4 Recruiting
Charlottesville, Virginia, United States, 22908-0334
Contact: Stacey L Williams    434-243-0425    Scw6n@hscmail.mcc.virginia.edu   
Principal Investigator: Patrick Dillon         
United States, Washington
Northwest Medical Specialties Dept of Onc Recruiting
Tacoma, Washington, United States, 98405
Contact: Elizabeth McGuire-Robinson    253-428-8752    bmcguire@nwmsonline.com   
Principal Investigator: Sibel Blau         
Argentina
Novartis Investigative Site Recruiting
Posadas, Misiones, Argentina
Novartis Investigative Site Recruiting
Rosario, Santa Fe, Argentina, S2000KZE
Novartis Investigative Site Recruiting
Rio Negro, Viedma, Argentina, 8500
Novartis Investigative Site Recruiting
Buenos Aires, Argentina, C1050AAK
Novartis Investigative Site Recruiting
Cordoba, Argentina, X5016KEH
Australia, New South Wales
Novartis Investigative Site Recruiting
Randwick, New South Wales, Australia, 2031
Novartis Investigative Site Recruiting
Wahroonga, New South Wales, Australia, 2076
Australia, Victoria
Novartis Investigative Site Recruiting
Malvern, Victoria, Australia, 3144
Novartis Investigative Site Recruiting
Parkville, Victoria, Australia, 3050
Belgium
Novartis Investigative Site Recruiting
Liege, Belgium, 4000
Brazil
Novartis Investigative Site Not yet recruiting
Salvador, BA, Brazil, 41253-190
Novartis Investigative Site Not yet recruiting
Fortaleza, CE, Brazil, 60430-230
Novartis Investigative Site Not yet recruiting
Natal, RN, Brazil, 59040-000
Novartis Investigative Site Recruiting
Passo Fundo, RS, Brazil, 99010-260
Novartis Investigative Site Recruiting
Porto Alegre, RS, Brazil, 90610-000
Novartis Investigative Site Recruiting
São Paulo, SP, Brazil, 01317-002
Novartis Investigative Site Not yet recruiting
São Paulo, Brazil, 01236-030
Denmark
Novartis Investigative Site Recruiting
Aarhus, Denmark, 8000 C
Novartis Investigative Site Recruiting
Copenhagen, Denmark, DK-2100
Novartis Investigative Site Withdrawn
Herlev, Denmark, DK-2730
Novartis Investigative Site Recruiting
Næstved, Denmark, DK-4700
Novartis Investigative Site Recruiting
Odense C, Denmark, DK-5000
Novartis Investigative Site Recruiting
Roskilde, Denmark, 4000
Novartis Investigative Site Recruiting
Vejle, Denmark, DK-7100
Hungary
Novartis Investigative Site Not yet recruiting
Budapest, Hungary, 1145
Novartis Investigative Site Recruiting
Debrecen, Hungary, 4032
Novartis Investigative Site Withdrawn
Gyor, Hungary, 9000
Novartis Investigative Site Recruiting
Nyiregyhaza, Hungary, 4400
Novartis Investigative Site Withdrawn
Szeged, Hungary, 6720
Novartis Investigative Site Recruiting
Tatabanya, Hungary, 2800
India
Novartis Investigative Site Recruiting
Hyderabad, Andhra Pradesh, India, 500 034
Novartis Investigative Site Recruiting
Pune, Maharashtra, India, 411013
Novartis Investigative Site Recruiting
Kolkatta, West Bengal, India, 700 053
Novartis Investigative Site Withdrawn
Kolkata, India, 700054
Novartis Investigative Site Recruiting
Mumbai, India, 400 012
Ireland
Novartis Investigative Site Recruiting
Limerick, Co Limerick, Ireland
Novartis Investigative Site Recruiting
Dublin 4, Ireland
Novartis Investigative Site Recruiting
Galway, Ireland
Lebanon
Novartis Investigative Site Recruiting
Beirut, Lebanon
Novartis Investigative Site Recruiting
Beirut, Lebanon, 1107 2020
Novartis Investigative Site Recruiting
Hazmieh, Lebanon, 470
Novartis Investigative Site Recruiting
Saida, Lebanon
Malaysia
Novartis Investigative Site Recruiting
Kota Kinabalu, Sabah, Malaysia, 88586
Novartis Investigative Site Recruiting
Kuala Lumpur, Malaysia, 59100
Peru
Novartis Investigative Site Recruiting
Jesus Maria, Lima, Peru, 11
Novartis Investigative Site Recruiting
San Borja, Lima, Peru, 41
Novartis Investigative Site Not yet recruiting
San Juan de Miraflores, Lima, Peru, 29
Novartis Investigative Site Recruiting
Surquillo, Lima, Peru, 34
Novartis Investigative Site Recruiting
Arequipa, Peru
Novartis Investigative Site Withdrawn
Arequipa, Peru
Russian Federation
Novartis Investigative Site Not yet recruiting
Arkhangelsk, Russian Federation, 163045
Novartis Investigative Site Not yet recruiting
Kazan, Russian Federation, 420029
Novartis Investigative Site Recruiting
Moscow, Russian Federation, 115998
Novartis Investigative Site Recruiting
Moscow, Russian Federation, 115478
Novartis Investigative Site Recruiting
St. Petersburg, Russian Federation, 197758
Saudi Arabia
Novartis Investigative Site Withdrawn
Dammam, Saudi Arabia, 15215
Novartis Investigative Site Withdrawn
Riyadh, Saudi Arabia, 11426
Novartis Investigative Site Withdrawn
Riyadh, Saudi Arabia, 11211
Spain
Novartis Investigative Site Recruiting
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Madrid, Spain, 28033
Novartis Investigative Site Recruiting
Madrid, Spain, 28040
Sweden
Novartis Investigative Site Recruiting
Eskilstuna, Sweden, SE-631 88
Novartis Investigative Site Recruiting
Gavle, Sweden, SE-801 87
Novartis Investigative Site Recruiting
Jönkoping, Sweden, 551 85
Novartis Investigative Site Withdrawn
Kalmar, Sweden, SE-391 85
Novartis Investigative Site Recruiting
Stockholm, Sweden, SE-171 76
Novartis Investigative Site Recruiting
Sundsvall, Sweden, 851 86
Novartis Investigative Site Recruiting
Uppsala, Sweden, SE-751 85
Novartis Investigative Site Recruiting
Vasteras, Sweden, 721 89
Novartis Investigative Site Recruiting
Växsjö, Sweden, SE-351 85
Thailand
Novartis Investigative Site Recruiting
Muang Lopburi, Lopburi, Thailand, 15000
Novartis Investigative Site Not yet recruiting
Bangkok, Thailand, 10400
Novartis Investigative Site Withdrawn
Bangkok, Thailand, 10210
Novartis Investigative Site Recruiting
Muang, Thailand, 40002
Novartis Investigative Site Recruiting
Songkla, Thailand, 90110
Turkey
Novartis Investigative Site Recruiting
Adana, Turkey, 01330
Novartis Investigative Site Recruiting
Istanbul, Turkey, 34303
Novartis Investigative Site Recruiting
Izmir, Turkey, 35340
United Kingdom
Novartis Investigative Site Recruiting
East Kilbride, United Kingdom, G75 8RG
Novartis Investigative Site Recruiting
Middlesborough, United Kingdom, TS4 3BW
Novartis Investigative Site Recruiting
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01783444     History of Changes
Other Study ID Numbers: CRAD001Y2201
Study First Received: January 11, 2013
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration
Europe: European Medicines Agency
Lebanon: Ministry of Public Health
Saudi Arabia: Ministry of Health
Sweden: Medical Products Agency
Turkey: Ministry of Health

Keywords provided by Novartis:
Estrogen receptor positive, locally advanced, metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Everolimus
Exemestane
Fluorouracil
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014