Clinical trial NCT03176238: Study in Post-menopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer
Official title: A Phase IIIb, Multi-center, Open-label Study of RAD001 in Combination With EXemestane in Post-menopausal Women With EStrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Locally Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post Menopausal Breast Cancer
Keywords: post menopausal
advanced breast cancer
metastatic breast cancer
everolimus
exemestane
mTor inhibitor
endocrine therapy
human epidermal growth factor
estrogen receptor positive
adult
CRAD001
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-06-05
Enrollment: 235
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This international, multi-center, open-label, single-arm study evaluated the safety and tolerability profile of everolimus in post-menopausal women with HR positive, HER2 negative locally advanced or metastatic breast cancer after documented recurrence or progression following a non-steroidal aromatase inhibitors (NSAI) therapy in Novartis Oncology emergent growth market (EGM) countries.Data was presented by Asian countries vs Non-Asian countries to confirm no difference in safety and efficacy. Summary statistics were presented.


Eligibility criteria: Inclusion Criteria:

* Postmenopausal women with metastatic, recurrent or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
* Histological or cytological confirmation of hormone-receptor positive (HR+) breast cancer.
* Disease refractory to non-steroidal aromatase inhibitors, defined as:
* Recurrence while on, or within 12 months (365 days) of completion of adjuvant therapy with letrozole or anastrozole, or
* Progression while on, or within one month (30 days) of completion of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer (ABC).
* Radiological or objective evidence of recurrence or progression on or after the last systemic therapy prior to enrolment.
* Patients must have had:
* At least one lesion that could have been accurately measured in at least one dimension

  * 20 mm with conventional imaging techniques or ≥ 10 mm with spiral CT or MRI, or
* Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above.
* Adequate bone marrow, coagulation, liver and renal function.
* ECOG performance status ≤ 2.

Exclusion Criteria:

* Patients overexpressing HER2 by local laboratory testing (IHC 3+ staining or in situ hybridization positive). Patients with IHC 2+ must have a negative in situ hybridization test.
* Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites).
* Patients with more than one prior chemotherapy line for ABC. A chemotherapy line is an anticancer regimen(s) that contained at least 1 cytotoxic chemotherapy agent, given for a minimum of 21 days.
* Previous treatment with mTOR inhibitors.
* Known hypersensitivity to mTOR inhibitors, e.g. Sirolimus (rapamycin).
* Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline was not required.
* Patient who were being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A
* History of brain or other CNS metastases, including leptomeningeal metastasis.

Primary outcomes:
measure: Summary of Number of Participants With Treatment Emergent Adverse Events (TEAE) - All Grades
timeFrame: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries including a 30 day post treatment follow up period
Secondary outcomes:
measure: Percentage of Participants Response Rates (Best Overall and Overall)
timeFrame: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries
measure: Percentage of Participants Clinical Benefit Rate
timeFrame: Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries
measure: Progression Free Survival (PFS)
timeFrame: Baseline up to approximately 43 weeks for Asian countires and 40 weeks for Non-Asian countries
measure: Percent of Participants Event-free Probability Estimates of Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Baseline up to approximately 50 weeks
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Novartis Investigative Site
state: Australian Capital Territory
city: Caringbah
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Liverpool
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Box Hill
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Ringwood East
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: St Albans
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Karamsad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Nashik
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Cuttack
country: India
facility: Novartis Investigative Site
state: Orissa
city: Bandung
country: Indonesia
facility: Novartis Investigative Site
city: Jakarta
country: Indonesia
facility: Novartis Investigative Site
city: Jogyakarta
country: Indonesia
facility: Novartis Investigative Site
city: Semarang
country: Indonesia
facility: Novartis Investigative Site
city: Amman
country: Jordan
facility: Novartis Investigative Site
city: Suwon
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi-do
city: Gyeonggi do
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Jeollanam-do
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Taegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: MYS
city: Kota Kinabalu
country: Malaysia
facility: Novartis Investigative Site
state: Sabah
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Wilayah Persekutuan
city: Casablanca
country: Morocco
facility: Novartis Investigative Site
city: Rabat
country: Morocco
facility: Novartis Investigative Site
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
state: Western Cape
city: George
country: South Africa
facility: Novartis Investigative Site
state: Western Cape
city: Western Cape
country: South Africa
facility: Novartis Investigative Site
city: New Taipei City
country: Taiwan
facility: Novartis Investigative Site
state: TWN
city: Changhua
country: Taiwan
facility: Novartis Investigative Site
city: Kaohsiung City
country: Taiwan
facility: Novartis Investigative Site
city: Kaoshiung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Ariana
country: Tunisia
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Gaziantep
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kartal
country: Turkey
facility: Novartis Investigative Site
city: Pendik / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: