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: October 18, 2013
Last verified: October 2013

March 16, 2009
October 18, 2013
June 2009
February 2011   (final data collection date for primary outcome measure)
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.
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 ]
Complete list of historical versions of study NCT00863655 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Breast Cancer
  • 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.
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
724
June 2014
February 2011   (final data collection date for primary outcome measure)

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

Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
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
 
NCT00863655
CRAD001Y2301, 2008-008698-69
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticlas Novartis Pharmaceuticals
Novartis
October 2013

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