Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole (BOLERO2)

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

Novartis ( Novartis Pharmaceuticals )

ClinicalTrials.gov Identifier:

NCT00863655

First received: March 16, 2009

Last updated: September 13, 2012

Last verified: September 2012

History of Changes

Tracking Information

First Received Date ^ICMJE

March 16, 2009

Last Updated Date

September 13, 2012

Start Date ^ICMJE

June 2009

Primary Completion Date

February 2011 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessments. [ Time Frame: 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, 27 July 2009, until cut-off date 11 February 2011. ] [ Designated as safety issue: No ]

Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.0). For patients with no target lesion, in the absence of new lesions, the overall lesion response at each assessment was one of following: Complete Response CR), Stable Disease SD), Unknown, or Progressive Disease (PD) based on non-target lesion responses. The following is considered progression among patients with lytic or mixed (lytic+sclerotic) bone lesions: appearance of ≥1 new lytic lesions in bone; the appearance of ≥ new lesions outside of bone and unequivocal progression of existing bone lesions.

Original Primary Outcome Measures ^ICMJE

progression-free survival (PFS), defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Change History

Complete list of historical versions of study NCT00863655 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Overall Survival (OS) [ Time Frame: Every 3 months after End of Treatment + 28 days (every 6 weeks before) ] [ Designated as safety issue: No ]
Overall survival, the key secondary endpoint in this study, is defined as the time from date of randomization to the date of death due to any cause.
Overall Response Rate (ORR) [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
ORR is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST.
Incidence of Adverse Events (AEs)/Serious Adverse Events (SAEs) [ Time Frame: Continuous and every 6 weeks ] [ Designated as safety issue: Yes ]
In addition to AEs/SAEs, shift from baseline in vital signs and laboratory results (hematology, blood chemistry) will be reported.
Qol Scores ECOG Performance Status [ Time Frame: Every 6 weeks ] [ Designated as safety issue: Yes ]
Change in QoL scores over time and time to deterioration of ECOG performance status.
Clinical Benefit Rate (CBR) [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
CBR is defined as the proportion of patients whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST.

Original Secondary Outcome Measures ^ICMJE

Overall survival (OS), the key secondary endpoint in this study, is defined as the time from date of randomization to the date of death due to any cause. [ Time Frame: Every 3 months after End of Treatment + 28 days (every 6 weeks before) ] [ Designated as safety issue: No ]
Overall response rate (ORR) defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
Incidence of adverse events, serious adverse events, shift from baseline in vital signs and laboratory results (hematology, blood chemistry) will be reported. [ Time Frame: Continuous and every 6 weeks ] [ Designated as safety issue: Yes ]
Patient reported outcome (PRO). [ Time Frame: Every 6 weeks ] [ Designated as safety issue: Yes ]
Clinical benefit rate (CBR) defined as the proportion of patients whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST. [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole

Official Title ^ICMJE

A Randomized Double-Blind, Placebo-Controlled Study of Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole

Brief Summary

There are no treatments specifically approved after recurrence or progression on a NSAI. In light of the need for new treatment options for postmenopausal women after failure of prior non steroidal aromatase inhibitors (NSAI) therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment with exemestane + everolimus to exemestane + placebo in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAI.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Breast Cancer

Intervention ^ICMJE

Drug: Everolimus
Everolimus was administered by continuous oral dosing of two 5-mg tablets.

Other Name: RAD001
Drug: Placebo
Placebo was formulated to be indistinguishable from the everolimus tablets.
Drug: Exemestane
Commercially available exemestane was supplied to sites as s25-mg tablets according to local regulations.

Study Arm (s)

Experimental: Everolimus + Exemestane
Everolimus 10 mg daily in combination with exemestane 25 mg daily
Interventions:
- Drug: Everolimus
- Drug: Exemestane
Active Comparator: Placebo + Exemestane
Placebo of everolimus in combination with exemestane 25 mg daily
Interventions:
- Drug: Placebo
- Drug: Exemestane

Publications *

Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. Epub 2011 Dec 7.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Enrollment ^ICMJE

724

Estimated Completion Date

June 2014

Primary Completion Date

February 2011 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
Postmenopausal women.
Disease refractory to non steroidal aromatase inhibitors (NSAI),
Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to randomization.
Patients must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease
Adequate bone marrow and coagulation function
Adequate liver and renal function
ECOG Performance Status = 2 or less

Exclusion Criteria:

HER2-overexpressing patients
Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.).
Patients who received more than one chemotherapy line for Advanced Breast Cancer.
Previous treatment with exemestane or mTOR inhibitors.
Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
Radiotherapy within four weeks prior to randomization
Currently receiving hormone replacement therapy,
Patients receiving immunosuppressive agents or chronic corticosteroids use
Patients being treated with strong inhibitors or inducers of CYP3A within 5 days prior to randomization

Other protocol-defined inclusion/exclusion criteria may apply

Gender

Female

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

United States, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Egypt, France, Germany, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Spain, Sweden, Thailand, Turkey, United Kingdom

Administrative Information

NCT Number ^ICMJE

NCT00863655

Other Study ID Numbers ^ICMJE

CRAD001Y2301, 2008-008698-69

Has Data Monitoring Committee

Not Provided

Responsible Party

Novartis ( Novartis Pharmaceuticals )

Study Sponsor ^ICMJE

Novartis Pharmaceuticals

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals
Study Director:	Novartis Pharmaceuticlas	Novartis Pharmaceuticals

Information Provided By

Novartis

Verification Date

September 2012

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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