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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/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 - Adverse events (AEs), serious adverse events (SAEs), changes from baseline in vital signs and laboratory results (hematology, blood chemistry, lipid profile) qualifying and reported as AEs. Although a patient might had two or more adverse events the patient is only counted once in a category. The same patient might appear in different categories. AESI: Adverse events of special interest.
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) - The best overall response for each patient is determined from the sequence of investigator overall lesion responses according to RECIST 1.1: Complete Response (CR)=disappearance of target lesions, Partial Response (PR) was >=30% decrease in sum of diameter of lesions, Progressive Disease (PD) was >=20% decrease in sum of diameter of lesions, Stable Disease (SD) does not qualify for PR, CR or PD, Unknown=not documented or assessed. To be assigned a best overall response of CR at least two determinations of CR at least 4 weeks apart before progression are required. To be assigned a best overall response of PR at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required. The Overall response rate (ORR) is the percentage of patients with a best overall response of confirmed complete (CR) or partial (PR) response. The 95% confidence intervals (CI) were computed using the Clopper-Pearson method
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 - Clinical benefit rate: Patients with best overall response rate of CR (any duration), PR (any duration) and SD with duration of 24 weeks or longer according to RECIST 1.1 criteria: Complete Response (CR)=disappearance of target lesions, Partial Response (PR) was >=30% decrease in sum of diameter of lesions, Progressive Disease (PD) was >=20% decrease in sum of diameter of lesions, Stable Disease (SD) does not qualify for PR, CR or PD, Unknown=not documented or assessed. Best overall response of CR = at least two determinations of CR at least 4 weeks apart before progression are required. Best overall response of PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) are required. The Overall response rate (ORR) is the percentage of patients with a best overall response of confirmed complete (CR) or partial (PR) response. The 95% confidence intervals (CI) were computed using the Clopper-Pearson method.
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) - PFS is time from date of start of treatment to date of disease progression or death due to any cause, whichever occurs first.
b Percentiles with 95% CIs are calculated from PROC LIFETEST output using method of Brookmeyer and Crowley (1982)
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 - Time to deterioration of ECOG performance status, from baseline will be assessed using the ECOG Performance Status Scale (Oken, 1982). Time to deterioration is the time from date of start of treatment to the date of the event defined as deterioration. Deterioration is defined as an increase in performance status from 0 to 2 or greater, an increase in performance status from 1-2 to 3 or greater, or death due to any cause. Event-free probability estimate is the estimated probability that a patient will remain event-free up to the specified time point. Event-free probability estimates were are obtained from the Kaplan-Meier survival estimates.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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/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
Other publications