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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03176238




Registration number
NCT03176238
Ethics application status
Date submitted
1/06/2017
Date registered
5/06/2017
Date last updated
7/04/2020

Titles & IDs
Public title
Study in Post-menopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer
Scientific 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
Secondary ID [1] 0 0
CRAD001JIC06
Universal Trial Number (UTN)
Trial acronym
EVEREXES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post Menopausal Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - everolimus
Treatment: Drugs - exemestane

Experimental: everolimus + exemestane - Everolimus (10 mg) and exemestane (25 mg) tablets taken orally in combination once daily


Treatment: Drugs: everolimus
one 10 mg tablet or two 5 mg tablets of everolimus were administered orally once daily on a continuous dosing schedule starting on Day 1

Treatment: Drugs: exemestane
25 mg tablet was administered orally once daily on a continuous dosing schedule starting on Day 1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Summary of Number of Participants With Treatment Emergent Adverse Events (TEAE) - All Grades
Timepoint [1] 0 0
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 outcome [1] 0 0
Percentage of Participants Response Rates (Best Overall and Overall)
Timepoint [1] 0 0
Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries
Secondary outcome [2] 0 0
Percentage of Participants Clinical Benefit Rate
Timepoint [2] 0 0
Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
Baseline up to approximately 43 weeks for Asian countires and 40 weeks for Non-Asian countries
Secondary outcome [4] 0 0
Percent of Participants Event-free Probability Estimates of Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status
Timepoint [4] 0 0
Baseline up to approximately 50 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/03/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/01/2019
Sample size
Target
Accrual to date
Final
235
Recruitment in Australia
Recruitment state(s)
ACT,NSW,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Garran
Recruitment hospital [2] 0 0
Novartis Investigative Site - Caringbah
Recruitment hospital [3] 0 0
Novartis Investigative Site - Liverpool
Recruitment hospital [4] 0 0
Novartis Investigative Site - Box Hill
Recruitment hospital [5] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [6] 0 0
Novartis Investigative Site - Ringwood East
Recruitment hospital [7] 0 0
Novartis Investigative Site - St Albans
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2229 - Caringbah
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
3135 - Ringwood East
Recruitment postcode(s) [7] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
India
State/province [1] 0 0
Gujarat
Country [2] 0 0
India
State/province [2] 0 0
Maharashtra
Country [3] 0 0
India
State/province [3] 0 0
Orissa
Country [4] 0 0
Indonesia
State/province [4] 0 0
Bandung
Country [5] 0 0
Indonesia
State/province [5] 0 0
Jakarta
Country [6] 0 0
Indonesia
State/province [6] 0 0
Jogyakarta
Country [7] 0 0
Indonesia
State/province [7] 0 0
Semarang
Country [8] 0 0
Jordan
State/province [8] 0 0
Amman
Country [9] 0 0
Korea, Republic of
State/province [9] 0 0
Gyeonggi-do
Country [10] 0 0
Korea, Republic of
State/province [10] 0 0
Korea
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seocho Gu
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Busan
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Jeollanam-do
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Taegu
Country [16] 0 0
Malaysia
State/province [16] 0 0
MYS
Country [17] 0 0
Malaysia
State/province [17] 0 0
Sabah
Country [18] 0 0
Malaysia
State/province [18] 0 0
Wilayah Persekutuan
Country [19] 0 0
Morocco
State/province [19] 0 0
Casablanca
Country [20] 0 0
Morocco
State/province [20] 0 0
Rabat
Country [21] 0 0
South Africa
State/province [21] 0 0
Western Cape
Country [22] 0 0
Taiwan
State/province [22] 0 0
TWN
Country [23] 0 0
Taiwan
State/province [23] 0 0
Changhua
Country [24] 0 0
Taiwan
State/province [24] 0 0
Kaohsiung City
Country [25] 0 0
Taiwan
State/province [25] 0 0
Kaoshiung
Country [26] 0 0
Taiwan
State/province [26] 0 0
Taipei
Country [27] 0 0
Thailand
State/province [27] 0 0
Bangkok
Country [28] 0 0
Thailand
State/province [28] 0 0
Chiang Mai
Country [29] 0 0
Tunisia
State/province [29] 0 0
Ariana
Country [30] 0 0
Turkey
State/province [30] 0 0
Ankara
Country [31] 0 0
Turkey
State/province [31] 0 0
Gaziantep
Country [32] 0 0
Turkey
State/province [32] 0 0
Izmir
Country [33] 0 0
Turkey
State/province [33] 0 0
Kartal
Country [34] 0 0
Turkey
State/province [34] 0 0
Pendik / Istanbul
Country [35] 0 0
Vietnam
State/province [35] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03176238
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03176238