A Study of Everolimus Plus Exemestane in Chinese Postmenopausal Women With Estrogen Receptor Positive, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Non-steroidal Aromatase Inhibitor

NCT03312738 | Completed Phase 2 Results

• 1 other identifier: CRAD001Y2202
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 15

Brief Summary

This study aimed at evaluating the safety and efficacy of everolimus plus exemestane in Chinese postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer after recurrence or progression on letrozole or anastrozole.

Conditions

Advanced Breast Cancer

Keywords

everolimus; exemestane; advanced Breast Cancer; non-steroidal aromatase inhibitors; breast carcinoma; breast cancer; breast lump; HER2 negative; breast cancer progression

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment

  PFS was defined as time from the date of randomization to the date of first documented progression or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. Disease progression was assessed using the local investigator's tumor assessment per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. The distribution of PFS was estimated using the Kaplan-Meier method. Cox regression model stratified by randomization stratification factors was used to estimate the hazard ratio (HR) of PFS, along with 90% CI. As this was an estimation based approach, no p-value was provided.

  From randomization up to date of first documented progression or death, assessed up to approximately 3.5 years

Secondary Outcomes (16)

• Progression-free Survival (PFS) Based on Blinded Independent Review Committee (BIRC) Assessment

  From randomization up to date of first documented progression or death, assessed up to approximately 1.8 years

• Overall Survival (OS)

  From randomization to date of death, up to approximately 3.8 years

• Overall Response Rate (ORR) Based on Local Radiology Review of Tumor Assessment

  Up to approximately 3.5 years

• Overall Response Rate (ORR) Based on BIRC Assessment

  Up to approximately 1.8 years

• Clinical Benefit Rate (CBR) Based on Local Radiology Review of Tumor Assessment

  Up to approximately 3.5 years

Study Arms (2)

Everolimus + Exemestane

EXPERIMENTAL

Participants received everolimus as a continuous oral daily dose of 10 mg and exemestane as a continuous oral daily dose of 25 mg

Drug: Everolimus; Drug: Exemestane

Placebo + Exemestane

ACTIVE COMPARATOR

Participants received placebo as a continuous oral daily dose and exemestane as a continuous oral daily dose of 25 mg

Drug: Exemestane; Drug: Everolimus Placebo

Interventions

Everolimus DRUG

Everolimus was formulated as tablets of 5 mg strength and was packaged into blister packs . Everolimus (two 5 mg tablets daily) was administered in a blinded manner by continuous oral daily dosing.

Also known as: RAD001

Everolimus + Exemestane

Exemestane DRUG

Commercially available exemestane was supplied as 25 mg tablets. Exemestane was administered as continuous oral daily dose of 25 mg tablets.

Everolimus + Exemestane; Placebo + Exemestane

Everolimus Placebo DRUG

Placebo was formulated to be indistinguishable from the everolimus tablets. Matching placebo (two tablets daily) was administered in a blinded manner by continuous oral daily dosing.

Placebo + Exemestane

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chinese Postmenopausal women with ER+ HER2- locally advanced, recurrent, or metastatic breast cancer. Locally advanced breast cancer must not be amenable to curative treatment by surgery or radiotherapy.
• Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
• Postmenopausal women. Postmenopausal status was defined either by:
• Prior bilateral oophorectomy
• Or age ≥60
• Or age \< 60 and amenorrhea for 12 or more months
• Recurrence or progression on prior NSAI was defined as:
• Recurrence while on, or within one year (12 months) of end of adjuvant treatment with letrozole or anastrozole
• Or Progression while on or within one month (30 days) of the end of prior treatment with letrozole or anastrozole
• Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrollment
• Patient had as per RECIST 1.1
• measurable disease or non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
• non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
• Patient was able to swallow and retain oral medication
• Patient met the hematologic and biochemistery laboratory values at the screening visit

You may not qualify if:

• HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive), based on the most recent test.
• Patients who had received more than one chemotherapy line for ABC
• Patients with symptomatic visceral disease and candidates to chemotherapy
• Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis (e.g. pleural effusion, ascites etc.)
• Patients receiving concomitant immunosuppressive agents or chronic corticosteroids used at the time of study entry except topical applications, inhaled sprays, eye drops or local injections.
• Uncontrolled diabetes mellitus as defined by HbA1c \>7% despite adequate therapy.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Guangzhou, Guangdong, 510000, China

Location

Novartis Investigative Site

Harbin, Heilongjiang, 150081, China

Location

Novartis Investigative Site

Wuhan, Hubei, 430022, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210009, China

Location

Novartis Investigative Site

Shanghai, Shanghai Municipality, 200032, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610072, China

Location

Novartis Investigative Site

Tianjin, Tianjin Municipality, 300060, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310022, China

Location

Novartis Investigative Site

Beijing, 100036, China

Location

Novartis Investigative Site

Chongqing, 400016, China

Location

Novartis Investigative Site

Guangzhou, 510060, China

Location

Novartis Investigative Site

Qingdao, 266000, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Wuhan, 430000, China

Location

Related Publications (1)

• Shao ZM, Cai L, Wang S, Hu X, Shen K, Wang H, Li H, Feng J, Liu Q, Cheng J, Wu X, Wang X, Li H, Luo T, Liu J, Amin K, Slimane K, Qiao Y, Liu Y, Tong Z. BOLERO-5: a phase II study of everolimus and exemestane combination in Chinese post-menopausal women with ER + /HER2- advanced breast cancer. Discov Oncol. 2024 Jun 21;15(1):237. doi: 10.1007/s12672-024-01027-8.

  PMID: 38904918 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2017
• First Posted: October 18, 2017
• Study Start: September 15, 2017
• Primary Completion: April 25, 2022
• Study Completion: April 25, 2022
• Last Updated: January 23, 2024
• Results First Posted: January 23, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (15)