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:
Novartis Pharmaceuticals
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
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Drug: Everolimus Drug: Placebo Drug: Exemestane |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | 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 |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- 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.
| Enrollment: | 724 |
| Study Start Date: | June 2009 |
| Estimated Study Completion Date: | June 2014 |
| Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Everolimus + Exemestane
Everolimus 10 mg daily in combination with exemestane 25 mg daily
|
Drug: Everolimus
Everolimus was administered by continuous oral dosing of two 5-mg tablets.
Other Name: RAD001
Drug: Exemestane
Commercially available exemestane was supplied to sites as s25-mg tablets according to local regulations.
|
|
Active Comparator: Placebo + Exemestane
Placebo of everolimus in combination with exemestane 25 mg daily
|
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.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00863655
Show 205 Study Locations
Show 205 Study LocationsSponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Study Director: | Novartis Pharmaceuticlas | Novartis Pharmaceuticals |
More Information
Additional Information:
No publications provided by Novartis
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT00863655 History of Changes |
| Other Study ID Numbers: | CRAD001Y2301, 2008-008698-69 |
| Study First Received: | March 16, 2009 |
| Results First Received: | July 31, 2012 |
| Last Updated: | September 13, 2012 |
| Health Authority: | United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Austria: Agency for Health and Food Safety Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment Brazil: National Health Surveillance Agency Canada: Health Canada Czech Republic: State Institute for Drug Control Egypt: Ministry of Health, Drug Policy and Planning Center France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Hong Kong: Department of Health Hungary: National Institute of Pharmacy Italy: National Institute of Health Japan: Pharmaceuticals and Medical Devices Agency Netherlands: Medicines Evaluation Board (MEB) New Zealand: Food Safety Authority Norway: Norwegian Medicines Agency Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products South Korea: Korea Food and Drug Administration (KFDA) Spain: Spanish Agency of Medicines Sweden: Medical Products Agency Thailand: Food and Drug Administration Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Novartis:
|
Breast Cancer Estrogen Receptor positive ER+ exemestane |
mTOR everolimus refractory NSAI |
Additional relevant MeSH terms:
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Estrogens Exemestane Letrozole Anastrozole Sirolimus Everolimus Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |
Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Aromatase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Antibiotics, Antineoplastic Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents Antineoplastic Agents, Hormonal |
ClinicalTrials.gov processed this record on May 22, 2013