Study in Post-menopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer

NCT03176238 | Completed Phase 3 Results

• 1 other identifier: CRAD001JIC06
• Study Type: interventional
• Target: 235
• Locations: 12 countries
• Sites: 54

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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 (4)

• Percentage of Participants Response Rates (Best Overall and Overall)

  Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries

• Percentage of Participants Clinical Benefit Rate

  Baseline up to approximately 43 weeks for Asian countires and 32 weeks for Non-Asian countries

• Progression Free Survival (PFS)

  Baseline up to approximately 43 weeks for Asian countires and 40 weeks for Non-Asian countries

• Percent of Participants Event-free Probability Estimates of Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status

  Baseline up to approximately 50 weeks

Study Arms (1)

everolimus + exemestane

EXPERIMENTAL

Everolimus (10 mg) and exemestane (25 mg) tablets taken orally in combination once daily

Drug: everolimus; Drug: exemestane

Interventions

everolimus DRUG

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

Also known as: RAD001

everolimus + exemestane

exemestane DRUG

25 mg tablet was administered orally once daily on a continuous dosing schedule starting on Day 1

everolimus + exemestane

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (55)

Novartis Investigative Site

Garran, Australian Capital Territory, 2605, Australia

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Novartis Investigative Site

Caringbah, New South Wales, 2229, Australia

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Novartis Investigative Site

Liverpool, New South Wales, 2170, Australia

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Novartis Investigative Site

Box Hill, Victoria, 3128, Australia

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Novartis Investigative Site

Heidelberg, Victoria, 3084, Australia

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Novartis Investigative Site

Ringwood East, Victoria, 3135, Australia

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Novartis Investigative Site

St Albans, Victoria, 3021, Australia

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Novartis Investigative Site

Karamsad, Gujarat, 388325, India

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Novartis Investigative Site

Nashik, Maharashtra, 422 004, India

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Novartis Investigative Site

Pune, Maharashtra, 411013, India

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Novartis Investigative Site

Cuttack, Odisha, 753 007, India

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Novartis Investigative Site

Bandung, 40161, Indonesia

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Novartis Investigative Site

Jakarta, 11420, Indonesia

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Novartis Investigative Site

Semarang, 50212, Indonesia

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Novartis Investigative Site

Yogyakarta, 55284, Indonesia

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Novartis Investigative Site

Amman, 11941, Jordan

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Novartis Investigative Site

Kuala Lumpur, Kuala Lumpur, 50586, Malaysia

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Novartis Investigative Site

Kuala Lumpur, MYS, 56000, Malaysia

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Novartis Investigative Site

Kota Kinabalu, Sabah, 88586, Malaysia

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Novartis Investigative Site

Casablanca, Morocco

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Novartis Investigative Site

Rabat, 6527, Morocco

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Novartis Investigative Site

Cape Town, Western Cape, 7925, South Africa

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Novartis Investigative Site

George, Western Cape, 6530, South Africa

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Novartis Investigative Site

Western Cape, Western Cape, 7925, South Africa

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Novartis Investigative Site

Suwon, Gyeonggi-do, 443380, South Korea

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Novartis Investigative Site

Jeollanam-do, Jeollanam-do, 519763, South Korea

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Novartis Investigative Site

Gyeonggi-do, Korea, 10408, South Korea

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Novartis Investigative Site

Seoul, Korea, 05505, South Korea

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Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

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Novartis Investigative Site

Busan, 602739, South Korea

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Novartis Investigative Site

Seoul, 01812, South Korea

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Novartis Investigative Site

Seoul, 02841, South Korea

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Novartis Investigative Site

Seoul, 03080, South Korea

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Novartis Investigative Site

Seoul, 03722, South Korea

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Novartis Investigative Site

Seoul, 06273, South Korea

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Novartis Investigative Site

Seoul, 06351, South Korea

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Novartis Investigative Site

Taegu, 41944, South Korea

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Novartis Investigative Site

Kaoshiung, Taiwan, 80756, Taiwan

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Novartis Investigative Site

New Taipei City, TWN, 23561, Taiwan

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Novartis Investigative Site

Changhua, 50006, Taiwan

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Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

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Novartis Investigative Site

Taipei, 10048, Taiwan

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Novartis Investigative Site

Taipei, 10449, Taiwan

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Novartis Investigative Site

Bangkok, 10300, Thailand

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Novartis Investigative Site

Bangkok, 10400, Thailand

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Novartis Investigative Site

Chiang Mai, 50200, Thailand

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Novartis Investigative Site

Aryanah, 2080, Tunisia

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Novartis Investigative Site

Pendik / Istanbul, Turkey, 34899, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06460, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06500, Turkey (Türkiye)

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Novartis Investigative Site

Gaziantep, 27310, Turkey (Türkiye)

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Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

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Novartis Investigative Site

Kartal, 34890, Turkey (Türkiye)

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Novartis Investigative Site

Ho Chi Minh City, 700000, Vietnam

Location

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

888-669-6682

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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 5, 2017
• Study Start: March 29, 2013
• Primary Completion: January 29, 2019
• Study Completion: January 29, 2019
• Last Updated: April 7, 2020
• Results First Posted: April 7, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share

Locations

VN (1); ID (4); MY (3); MO (2); ZA (3); TH (3); TU (7); IN (4); JO (1); AU (7); TW (6); KR (13)