Open-label, Phase II, Study of Everolimus Plus Letrozole in Postmenopausal Women With ER+, HER2- Metastatic or Locally Advanced Breast Cancer

NCT ID: NCT01698918

Last Updated: 2023-05-03

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

202 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-07

Study Completion Date

2021-01-13

Brief Summary

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The purpose of this study was to assess the efficacy and safety of first-line treatment with everolimus plus letrozole in postmenopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer.

Moreover, the study also aimed to investigate the efficacy and safety of second line treatment with everolumus plus examestane in participants whose disease progressed during everolimus plus letrozole therapy.

Detailed Description

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This was an open-label, phase II, multicenter, international, single-arm study for postmenopausal women with ER+/HER2- metastatic or locally advanced breast cancer.

This study was comprised of 2 phases:

\- Core Phase: from first participant first visit to 24 months after enrollment of the last participant (and upon approval of amendment 5 dated 14-Feb-2017), up to approximately 4 years. The main purpose of the amendment 5 was to implement an Extension Phase up to 3 years.

During the core phase, all enrolled participants received everolimus in combination with letrozole in the first line setting until disease progression or any other reason for which the participant might be discontinued. Only those participants who had disease progression in the first line setting were offered second line treatment (everolimus in combination with exemestane). Participants who discontinued first line treatment due to reasons other than disease progression were not eligible for second line treatment. The participants who were treated in the second line setting continued treatment until disease progression, unacceptable toxicity or withdrawal of consent.

\- Extension Phase: Participants that were still benefiting from everolimus at the end of the Core Phase (and upon approval of amendment 5 dated 14-Feb-2017) were transitioned to the Extension phase of the study. Participants were continued on their existing line of treatment (everolimus plus letrozole or everolimus plus exemestane) in the extension, up to 3 years or until progression or any other reason for which the participant might be discontinued. Participants entering the Extension Phase on first line treatment and deemed to no longer be clinically benefiting were not offered second line treatment in the context of the study

This study included a randomized, open-label sub-study for participants in countries where the alcohol-free 0.5mg/5ml dexamethasone oral solution was commercially available who experienced a stomatitis event: at the first onset of symptoms suggestive of stomatitis, participants were to contact the study site and based on preliminary confirmation of diagnosis, participants were asked to visit the study site within 24 hours. Upon confirmation of stomatitis, participants in countries where the alcohol-free 0.5 mg/5 mL dexamethasone oral solution was commercially available (US sites only) were randomly assigned in a 1:1 ratio to take either 0.5 mg/5 mL dexamethasone mouth rinse or the standard of care used to treat stomatitis at the participant's center.

All participants who experienced stomatitis (regardless of inclusion in the sub-study) were instructed to fill out the Oral Stomatitis Daily Questionnaire (OSDQ) at home every day until the participant recovered. For subsequent episodes of stomatitis, participants were instructed to contact the physician. If part of the randomized set upon telephone confirmation, they were instructed to utilize the same treatment they were assigned to after the first episode and complete the OSDQ booklet.

Conditions

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Hormone Receptor Positive Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

The main study was an open-label single-arm study. The stomatitis sub-study was a randomized open-label study with two arms: dexamethasone and standard of care.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Everolimus+letrozole/exemestane (first line and second line treatment)

Participants received everolimus in combination with letrozole as first-line treatment. Only participants who had disease progression in the first line setting (core phase) were offered second-line treatment (everolimus in combination with exemestane)

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

Everolimus was self-administered as a daily dose of 10mg (two 5mg tablets) taken orally continuously until progression of disease, unacceptable toxicity or withdrawal of consent.

Letrozole

Intervention Type DRUG

1st line study treatment: Letrozole was self administered as a daily dose of 2.5mg continuously until disease progression or any other reason for which the patient might be discontinued

Exemestane

Intervention Type DRUG

2nd Line Study Treatment: Exemestane was self administered as a daily dose of 25mg taken orally continuously until disease progression or any other reason for which the patient might be discontinued

Alcohol-free dexamethasone mouth rinse (Stomatitis sub-study)

Intervention Type DRUG

Alcohol-free 0.5mg/5ml dexamethasone oral solution was self-administered at a daily dose of 10ml 3 times per day (participants with confirmed stomatitis who entered the stomatitis sub-study).

Standard of care to treat stomatitis (Stomatitis sub-study)

Intervention Type DRUG

Standard of care used to treat stomatitis at the patient's center (participants with confirmed stomatitis who entered the stomatitis sub-study).

Interventions

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Everolimus

Everolimus was self-administered as a daily dose of 10mg (two 5mg tablets) taken orally continuously until progression of disease, unacceptable toxicity or withdrawal of consent.

Intervention Type DRUG

Letrozole

1st line study treatment: Letrozole was self administered as a daily dose of 2.5mg continuously until disease progression or any other reason for which the patient might be discontinued

Intervention Type DRUG

Exemestane

2nd Line Study Treatment: Exemestane was self administered as a daily dose of 25mg taken orally continuously until disease progression or any other reason for which the patient might be discontinued

Intervention Type DRUG

Alcohol-free dexamethasone mouth rinse (Stomatitis sub-study)

Alcohol-free 0.5mg/5ml dexamethasone oral solution was self-administered at a daily dose of 10ml 3 times per day (participants with confirmed stomatitis who entered the stomatitis sub-study).

Intervention Type DRUG

Standard of care to treat stomatitis (Stomatitis sub-study)

Standard of care used to treat stomatitis at the patient's center (participants with confirmed stomatitis who entered the stomatitis sub-study).

Intervention Type DRUG

Other Intervention Names

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RAD001 Femara Aromasin

Eligibility Criteria

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Inclusion Criteria

* Patients with metastatic or locally advanced, unresectable breast cancer not amenable to curative treatment by surgery or radiotherapy
* Histological or cytological confirmation of ER+/ HER2- breast cancer
* Postmenopausal women
* No prior treatment for metastatic breast cancer

Exclusion Criteria

* Patients with only non-measurable lesions other than bone metastases (e.g., pleural effusion, ascites, etc)
* Patients who had received prior hormonal or any other systemic therapy for metastatic breast cancer. Patients might have received prior neoadjuvant or adjuvant endocrine therapy. In the case of neoadjuvant or adjuvant NSAI (letrozole/anastrozole) therapy patients must have completed therapy at least 1 year prior to study enrollment.
* Previous treatment with mTOR inhibitors.
* Known hypersensitivity to mTOR inhibitors, e.g., sirolimus (rapamycin).
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of Alabama Comprehensive Cancer Center SC-2

Birmingham, Alabama, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Loma Linda University Loma Linda

Loma Linda, California, United States

Site Status

Breastlink Medical Group Dept. of BreastlinkResearchGrp

Long Beach, California, United States

Site Status

Oncology Specialists, SC Advocate Medical Group-Niles

Park Ridge, Illinois, United States

Site Status

St. Francis Health Comprehensive Cancer Center

Topeka, Kansas, United States

Site Status

Norton Healthcare Inc SC

Louisville, Kentucky, United States

Site Status

Baystate Medical Center SC-2

Springfield, Massachusetts, United States

Site Status

Saint Barnabas Medical Center CancerCenter of Saint Barnabas

Livingston, New Jersey, United States

Site Status

University of New Mexico Hospital SC

Albuquerque, New Mexico, United States

Site Status

Broome Oncology SC

Johnson City, New York, United States

Site Status

Columbia University Medical Center- New York Presbyterian Columbia

New York, New York, United States

Site Status

Cone Health Cancer Center

Greensboro, North Carolina, United States

Site Status

East Texas Hematology Clinic SC

Lufkin, Texas, United States

Site Status

Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)

Salt Lake City, Utah, United States

Site Status

Novartis Investigative Site

Santa Rosa, La Pampa Province, Argentina

Site Status

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

Site Status

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Site Status

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Site Status

Novartis Investigative Site

Besançon, , France

Site Status

Novartis Investigative Site

Bordeaux, , France

Site Status

Novartis Investigative Site

Hyères, , France

Site Status

Novartis Investigative Site

Le Chesnay, , France

Site Status

Novartis Investigative Site

Lyon, , France

Site Status

Novartis Investigative Site

Nancy, , France

Site Status

Novartis Investigative Site

Nantes, , France

Site Status

Novartis Investigative Site

Kecskemét, Bács-Kiskun county, Hungary

Site Status

Novartis Investigative Site

Gyula, , Hungary

Site Status

Novartis Investigative Site

Szekszárd, , Hungary

Site Status

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Site Status

Novartis Investigative Site

Sapporo, Hokkaido, Japan

Site Status

Novartis Investigative Site

Shiwa-gun, Iwate, Japan

Site Status

Novartis Investigative Site

Kawasaki, Kanagawa, Japan

Site Status

Novartis Investigative Site

Kumamoto, Kumamoto, Japan

Site Status

Novartis Investigative Site

Maastricht, AZ, Netherlands

Site Status

Novartis Investigative Site

Lisbon, , Portugal

Site Status

Novartis Investigative Site

Lisbon, , Portugal

Site Status

Novartis Investigative Site

Porto, , Portugal

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Salamanca, Castille and León, Spain

Site Status

Novartis Investigative Site

A Coruña, Galicia, Spain

Site Status

Novartis Investigative Site

Valencia, Valencia, Spain

Site Status

Novartis Investigative Site

Bangkok, , Thailand

Site Status

Novartis Investigative Site

Bangkok, , Thailand

Site Status

Novartis Investigative Site

Bangkok, , Thailand

Site Status

Novartis Investigative Site

Antalya, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Istanbul, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Izmir, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Bath, , United Kingdom

Site Status

Countries

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United States Argentina Brazil France Hungary Japan Netherlands Portugal South Korea Spain Thailand Turkey (Türkiye) United Kingdom

References

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Royce M, Bachelot T, Villanueva C, Ozguroglu M, Azevedo SJ, Cruz FM, Debled M, Hegg R, Toyama T, Falkson C, Jeong J, Srimuninnimit V, Gradishar WJ, Arce C, Ridolfi A, Lin C, Cardoso F. Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Clinical Trial. JAMA Oncol. 2018 Jul 1;4(7):977-984. doi: 10.1001/jamaoncol.2018.0060.

Reference Type DERIVED
PMID: 29566104 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2012-003065-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001Y24135

Identifier Type: -

Identifier Source: org_study_id

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