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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01783444
Recruitment Status : Active, not recruiting
First Posted : February 5, 2013
Last Update Posted : November 29, 2017
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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 or disease Intervention/treatment Phase
Breast Cancer Drug: Capecitabine Drug: Exemestane Drug: Everolimus Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 317 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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.
Actual Study Start Date : February 26, 2013
Actual Primary Completion Date : June 1, 2017
Estimated Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 28 months after first patient randomized or once 150 PFS have occurred ]
    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 :
  1. Overall Survival [ Time Frame: Every 3 months following the end of study visit until 2015 (up to 3 years) ]
    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.

  2. 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 ]
    Overall response rate (ORR) based on the local radiologist/investigator's tumor assessment (RECIST 1.1)

  3. 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 ]
    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.

  4. Changes in ECOG (Eastern Cooperative Oncology Group) performance status [ Time Frame: Baseline, Day 1, every 6 weeks for approximately 8 months ]
    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.

  5. Change in quality of life scores over time: EORTC (QLQ-C30)/EORTC module (BR23) [ Time Frame: Baseline, every 6 weeks for approximately 8 months ]
  6. Time to quality of life (QoL)deterioration : TSQM score [ Time Frame: Baseline, week 3,6, 12 for approximately 8 months ]
  7. Safety: Incidence of Adverse Event(s) [ Time Frame: every study visit for approximately 8 months ]
  8. Safety: Incidence of Serious Adverse Events [ Time Frame: every study visit for approximately 8 months ]
  9. Safety: changes in vital signs when compared to baseline vital signs [ Time Frame: baseline, every study visit for approximately 8 months ]
  10. Safety: changes in laboratory values compared to laboratory values obtained at the baseline visit [ Time Frame: baseline, every study visit for approximately 8 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01783444

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United States, California
University of California at Los Angeles Mattel Children's Hospital
Los Angeles, California, United States, 90095
University of California - Davis SC
Sacramento, California, United States, 95817
Sharp Memorial Hospital SharpClinicalOncologyResearch
San Diego, California, United States, 92123
United States, Florida
Florida Cancer Specialists Dept of Oncology (2)
Fort Myers, Florida, United States, 33901
Florida Cancer Specialists FL Cancer Specialists
Fort Myers, Florida, United States, 33901
United States, Maryland
Carroll Regional Cancer Center
Westminster, Maryland, United States, 21157
United States, Massachusetts
Lahey Clinic Dept of Lahey Clinic (2)
Burlington, Massachusetts, United States, 01805
New England Hematology/ Oncology Associates, P.C. SC
Newton, Massachusetts, United States, 02462
United States, Montana
Glacier View Research Institute - Cancer SC
Kalispell, Montana, United States, 59901
United States, New Jersey
Trinitas Comprehensive Cancer Center SC
Elizabeth, New Jersey, United States, 07207
Hackensack University Medical Center Dept of Oncology
Hackensack, New Jersey, United States, 07601
Rutgers-New Jersey Medical School SC
Newark, New Jersey, United States, 07101
United States, Ohio
Oncology Hematology Care, Inc. Oncology Hematology Care (2)
Cincinnati, Ohio, United States, 45242
United States, Oklahoma
Oklahoma Cancer Specialists and Research Institute Oklahoma Cancer Specialists
Tulsa, Oklahoma, United States, 74136
United States, Tennessee
Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
Chattanooga, Tennessee, United States, 37404
The Jones Clinic SC
Germantown, Tennessee, United States, 38138
University of Tennessee SC
Knoxville, Tennessee, United States, 27920-6969
Sarah Cannon Research Institute SC (2)
Nashville, Tennessee, United States, 37203
United States, Texas
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD
Fort Worth, Texas, United States, 76104
United States, Virginia
University of Virginia Health Systems SC-4
Charlottesville, Virginia, United States, 22908-0334
United States, Washington
Northwest Medical Specialties Dept of Onc
Tacoma, Washington, United States, 98405
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Caba, Buenos Aires, Argentina, C1025ABI
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Posadas, Misiones, Argentina
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Aarhus, Denmark, 8000 C
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Odense C, Denmark, DK-5000
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Budapest, HUN, Hungary, 1145
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Debrecen, Hungary, 4032
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Pune, Maharashtra, India, 411013
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Arkhangelsk, Russian Federation, 163045
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Moscow, Russian Federation, 115478
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St. Petersburg, Russian Federation, 197758
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Sevilla, Andalucia, Spain, 41013
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Madrid, Spain, 28033
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Eskilstuna, Sweden, SE-631 88
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Joenkoeping, Sweden, 551 85
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Stockholm, Sweden, SE-171 76
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Uppsala, Sweden, SE-751 85
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Vasteras, Sweden, 721 89
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Vaxjo, Sweden, SE-351 85
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Muang Lopburi, Lopburi, Thailand, 15000
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Bangkok, Thailand, 10400
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Muang, Thailand, 40002
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Songkla, Thailand, 90110
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Adana, Turkey, 01330
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Istanbul, Turkey, 34303
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Izmir, Turkey, 35340
United Kingdom
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East Kilbride, United Kingdom, G75 8RG
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Middlesborough, United Kingdom, TS4 3BW
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Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals Identifier: NCT01783444     History of Changes
Other Study ID Numbers: CRAD001Y2201
First Posted: February 5, 2013    Key Record Dates
Last Update Posted: November 29, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists