Clinical trial NCT03312738: 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
Official title: A Randomized, Double-blind, Placebo Controlled, Phase II Study of Everolimus in Combination With Exemestane in the Treatment of Chinese Postmenopausal Women With Estrogen Receptor Positive, HER-2 Negative, Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Prior Letrozole or Anastrozole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-10-18
Enrollment: 159
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This was a multicenter, double-blind, randomized, placebo-controlled, phase II study evaluating treatment with everolimus (10 mg daily) in combination with exemestane (25 mg daily) vs placebo in combination with exemestane (25 mg daily) in Chinese postmenopausal women with locally advanced, recurrent or metastatic ER+ HER2- breast cancer refractory to non-steroidal aromatase inhibitors.

Randomized participants started the study treatment at Cycle 1 Day 1, and were treated continuously until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death or discontinuation from treatment for any other reason.

After end of treatment, all participants were followed up for safety up to 30 days after last dose of study treatment (exemestane and/or everolimus/placebo). All participants were followed for survival status at least every 3 months after treatment discontinuation unless they discontinued due to death, consent withdrawal or lost to follow-up

If a participants permanently discontinued study treatment for reasons other than disease progression, death, lost to follow-up, or withdrawal of consent to efficacy follow-up then they entered the post-treatment efficacy follow-up period until disease progression, death, lost to follow-up or withdrawal of consent for efficacy follow-up.

Eligibility criteria: Key Inclusion Criteria:

* 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
* Patient had a WHO performance status ≤2
* Written informed consent obtained prior to any screening procedures

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Progression-free Survival (PFS) Based on Local Radiology Review of Tumor Assessment
timeFrame: From randomization up to date of first documented progression or death, assessed up to approximately 3.5 years
Secondary outcomes:
measure: Progression-free Survival (PFS) Based on Blinded Independent Review Committee (BIRC) Assessment
timeFrame: From randomization up to date of first documented progression or death, assessed up to approximately 1.8 years
measure: Overall Survival (OS)
timeFrame: From randomization to date of death, up to approximately 3.8 years
measure: Overall Response Rate (ORR) Based on Local Radiology Review of Tumor Assessment
timeFrame: Up to approximately 3.5 years
measure: Overall Response Rate (ORR) Based on BIRC Assessment
timeFrame: Up to approximately 1.8 years
measure: Clinical Benefit Rate (CBR) Based on Local Radiology Review of Tumor Assessment
timeFrame: Up to approximately 3.5 years
measure: Clinical Benefit Rate (CBR) Based on BIRC Assessment
timeFrame: Up to approximately 1.8 years
measure: Time to Response (TTR) Based on Local Radiology Review of Tumor Assessment
timeFrame: Up to approximately 3.5 years
measure: Time to Response (TTR) Based on BIRC Assessment
timeFrame: Up to approximately 1.8 years
measure: Duration of Response (DOR) Based on Local Radiology Review of Tumor Assessment
timeFrame: From date of first documented response to date of first documented disease progression or death, assessed up to approximately 3.5 years
measure: Duration of Response (DOR) Based on BIRC Assessment
timeFrame: From date of first documented response to date of first documented disease progression or death, assessed up to approximately 1.8 years
measure: Time to Definitive Deterioration of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score From Baseline
timeFrame: From randomization up to definitive deterioration of the ECOG PS by one categotu of the score, assessed up to approximately 3.5 years
measure: Everolimus Predose Concentration (Cmin)
timeFrame: Predose on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
measure: Everolimus Concentration at 2 Hours Post Dose (C2h)
timeFrame: Two hours post everolimus administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
measure: Exemestane Predose Concentration (Cmin)
timeFrame: Predose of exemestane on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
measure: Exemestane Concentration at 2 Hours Post Dose (C2h)
timeFrame: Two hours post exemestane administration on Cycle 1 Week 4 ( each cycle is defined as 4 weeks)
measure: Estradiol Levels After 4 Weeks of Study Treatment
timeFrame: Baseline, and at Cycle 1 Week 4 prior to any study drug (each cycle is defined as 4 weeks)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Harbin
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Tianjin
country: China
facility: Novartis Investigative Site
state: Tianjin
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
city: Qingdao
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Wuhan
country: China
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: