A clinical study of everolimus in combination with letrozole in the treatment of postmenopausal women with estrogen receptor positive metastatic breast cancer

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2012-003065-17-ES
• Date of registration: 09/04/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Farmacéutica S.A.
• Public title: A clinical study of everolimus in combination with letrozole in the treatment of postmenopausal women with estrogen receptor positive metastatic breast cancer
• Scientific title: An open-label, phase II, single-arm study of everolimus in combination with letrozole in the treatment of postmenopausal women with estrogen receptor positive metastatic breast cancer - BOLERO-4
• Date of first enrolment: 24/05/2013
• Target sample size: 158
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003065-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: yes; Single blind: no; Double blind: no; Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, France, Hungary, Japan, Korea, Republic of, Netherlands, Portugal, Spain, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Departamento Médico Oncología (GMO)
• Affiliation: Novartis Farmacéutica S.A.

• Name: Departamento Médico Oncología (GMO)
• Affiliation: Novartis Farmacéutica S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
?Patients 18 years old or greater
?Patients with metastatic or locally advanced, unresectable breast cancer not amenable to curative treatment by surgery or radiotherapy
?Histological or cytological confirmation of estrogen-receptor positive (ER+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer
?Postmenopausal women
?No prior treatment for metastatic breast cancer

Other protocol based inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 142
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 87

Exclusion criteria:
?Patients with only non-measurable lesions other than bone metastases (e.g., pleural effusion, ascites, etc)
?Patients who have received prior hormonal or any other systemic therapy for metastatic breast cancer.
?Patients may have received prior neoadjuvant or adjuvant endocrine therapy. In the case of neoadjuvant or adjuvant NSAI (letrozole/anastrozole) therapy patients must have completed therapy at least 1 year prior to study enrollment.
?Previous treatment with mTOR inhibitors.
?Known hypersensitivity to mTOR inhibitors, e.g., sirolimus (rapamycin).
?Other protocol-defined inclusion/exclusion criteria may apply

Other protocol based exclusion criteria may apply


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Estrogen receptor positive metastatic breast cancer
MedDRA version: 14.1 Level: LLT Classification code 10070577 Term: Oestrogen receptor positive breast cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Afinitor
Product Name: Everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Exemestano
Pharmaceutical Form: Coated tablet
INN or Proposed INN: EXEMESTANO
CAS Number: 107868-30-4
Other descriptive name: EXEMESTANO
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Femara
Product Name: Femara
Product Code: FEM345
Pharmaceutical Form: Tablet
INN or Proposed INN: LETROZOL
CAS Number: 112809-51-5
Current Sponsor code: FEM345
Other descriptive name: LETROZOL
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Product Name: Dexametasona 0.5mg/5ml
Pharmaceutical Form: Oral solution
INN or Proposed INN: DEXAMETASONA
CAS Number: 50-02-2
Current Sponsor code: DEXAMETASONA
Other descriptive name: DEXAMETASONA
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.5mg/5ml-

Primary Outcome(s)

Primary end point(s): Percentage of patients progression-free after completion of 1st line treatment (everolimus + letrozole)

Main Objective: The primary objective is to estimate progression-free survival in patients treated with everolimus + letrozole in the first line metastatic setting.

Secondary Objective: - Determine the overall response rate and clinical benefit rate of everolimus + letrozole in the first line metastatic setting
- Determine the progression free survival and clinical benefit rate of everolimus + exemestane in second line population
- Estimate the overall survival of patients treated with everolimus + letrozole in the first line setting
- Evaluate a therapeutic intervention to reduce the severity and duration of stomatitis
- Evaluate the safety of everolimus + letrozole in the first line setting
- Evaluate the safety of everolimus + exemestane in the second line setting

Timepoint(s) of evaluation of this end point: 12 months after last patient recruited

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - Baseline, every 8 weeks
- Baseline, every 8 weeks
- Baseline, every 8 weeks
- Upon onset of 1st stomatitis, patient will complete diary daily until resolution of stomatitis
- Continuous during the study, up to 28 days after last treatment

Secondary end point(s): - Overall response rate in patients receiving the first line study treatment (everolimus + letrozole)
- Progression-free survival in the second line is defined as the time interval between start of 2nd line treatment and documented disease progression or death due to any cause reported during or after second-line treatment
- Overall survival of patients receiving first line study treatment (everolimus + letrozole)
- Reduction in severity and duration of oral stomatitis
- Assessment of safety based on the frequency of adverse events that fall outside normal pre-specified ranges

Secondary ID(s)

CRAD001Y24135

2012-003065-17-GB

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 09/04/2013
Contact:

Results

• Results available: Yes
• Date Posted: 28/01/2022
• Date Completed: 13/01/2021
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-003065-17/results