Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer

NCT ID: NCT03822468

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 376 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-11
• Study Completion Date: 2024-08-30

Brief Summary

The purpose of the study was to evaluate the safety and efficacy of a reduced ribociclib starting dose of 400 mg in combination with a non-steroidal aromatase inhibitor (NSAI) (letrozole or anastrozole) for the treatment of pre- and postmenopausal women with hormone receptor-positive (HR-positive), HER2-negative advanced breast cancer (aBC) who have received no prior therapy for advanced disease. Premenopausal women were required to receive goserelin in both treatment arms.

Detailed Description

Patients were assigned at visit Cycle 1 Day 1 to one of the following two treatment arms in a ratio of 1:1:

• Experimental arm: Ribociclib 400 mg (2 × 200 mg tablets by mouth) QD on Days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (Days 22 to 28) in combination with ET consisting of:

• For postmenopausal women:
• Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously

• For premenopausal women:
• Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously, combined with goserelin 3.6 mg subcutaneously once every 4 weeks.
• Control arm: Ribociclib 600 mg (3 × 200 mg tablets by mouth) QD on Days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (Days 22 to 28) in combination with ET consisting of:

• For postmenopausal women:

~ Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously.

• For premenopausal women:

• Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously, combined with goserelin 3.6 mg subcutaneously once every 4 weeks.

Participants received study treatment until disease progression (radiologically documented according to RECIST 1.1 criteria), unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

For participants who discontinued treatment for reasons other than documented disease progression, death, lost to follow-up, or withdrawal of consent, tumor assessments continued to be performed until disease progression, death, lost to follow-up, or withdrawal of consent (post-treatment efficacy follow-up).

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ribociclib 400 mg

Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)

Group Type: EXPERIMENTAL

Ribociclib

Intervention Type: DRUG

Ribociclib (at a dosage of 400 mg or 600 mg) QD orally taken on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (days 22 to 28). Ribociclib was supplied as 200 mg tablets as individual patient supply packaged bottles.

Anastrozole

Intervention Type: DRUG

Anastrozole 1 mg tablets for oral use QD continuously

Letrozole

Intervention Type: DRUG

Letrozole 2.5 mg tablets for oral use QD continuously

Goserelin

Intervention Type: DRUG

Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

Ribociclib 600 mg

Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)

Group Type: ACTIVE_COMPARATOR

Ribociclib

Intervention Type: DRUG

Ribociclib (at a dosage of 400 mg or 600 mg) QD orally taken on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (days 22 to 28). Ribociclib was supplied as 200 mg tablets as individual patient supply packaged bottles.

Anastrozole

Intervention Type: DRUG

Anastrozole 1 mg tablets for oral use QD continuously

Letrozole

Intervention Type: DRUG

Letrozole 2.5 mg tablets for oral use QD continuously

Goserelin

Intervention Type: DRUG

Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

Interventions

Ribociclib

Ribociclib (at a dosage of 400 mg or 600 mg) QD orally taken on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (days 22 to 28). Ribociclib was supplied as 200 mg tablets as individual patient supply packaged bottles.

Intervention Type: DRUG

Anastrozole

Anastrozole 1 mg tablets for oral use QD continuously

Intervention Type: DRUG

Letrozole

Letrozole 2.5 mg tablets for oral use QD continuously

Intervention Type: DRUG

Goserelin

Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

Intervention Type: DRUG

Other Intervention Names

LEE011

Eligibility Criteria

Inclusion Criteria

• Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable to curative therapy.
• Patient has a histologically and/or cytologically confirmed diagnosis of ER-positive and/or PgR-positive breast cancer based on the most recently analyzed tissue sample, and all tested by local laboratory.
• Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample.
• Patient must have measurable disease, i.e., at least one measurable lesion according to RECIST version 1.1. (a lesion in a previously irradiated site may only be counted as a target lesion if there is clear evidence of progression since the irradiation).
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory:

• QTcF interval at screening < 450 ms (QT interval using Fridericia's correction)
• Mean resting heart rate 50 to 90 bpm (determined from the ECG)
• Women of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant, must have confirmed negative serum pregnancy test (for β-hCG) within 14 days prior to randomization.
• Women of CBP must be willing to use highly effective methods of contraception.

Exclusion Criteria

• Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's judgment.
• Patient who received any prior systemic anti-cancer therapy(including endocrine therapy, chemotherapy, prior CDK4/6 inhibitors) for aBC. Patients who received neo-/adjuvant therapy for breast cancer are eligible.
• Patient is concurrently using other anti-cancer therapy.
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major toxicities.
• Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization, and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). Patients in whom ≥
• 25% of the bone marrow has been previously irradiated are also excluded.
• Patient has a concurrent malignancy or malignancy within 3 years of the randomization date, with the exception of adequately treated basal or squamous cell skin carcinoma, or curatively resected cervical carcinoma in situ.
• Patients with central nervous system (CNS) involvement unless they meet specific stability criteria.
• Patient has clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
• Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, and has not fully recovered from side effects of such treatment.

Other protocol-defined Inclusion/Exclusion may apply.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Southern Cancer Center PC

Mobile, Alabama, United States

Marin Cancer Care

Greenbrae, California, United States

Rocky Mountain Cancer Centers

Longmont, Colorado, United States

Florida Retina Institute

Orlando, Florida, United States

Weinberg Cancer Institute at FSH

Baltimore, Maryland, United States

Nebraska Hematology Oncology P C

Lincoln, Nebraska, United States

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Comprehensive Cancer Cntr Of Nevada

Henderson, Nevada, United States

New York Oncology Hematology

Albany, New York, United States

Mount Sinai School Of Medicine

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Millennium Research Clin Develop

Houston, Texas, United States

Texas Oncology

McAllen, Texas, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Novartis Investigative Site

San Juan, , Argentina

Novartis Investigative Site

Innsbruck, Tyrol, Austria

Novartis Investigative Site

Linz, , Austria

Novartis Investigative Site

Salzburg, , Austria

Novartis Investigative Site

Vienna, , Austria

Novartis Investigative Site

Edegem, , Belgium

Novartis Investigative Site

Namur, , Belgium

Novartis Investigative Site

Natal, Rio Grande do Norte, Brazil

Novartis Investigative Site

Florianópolis, Santa Catarina, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

Goiânia, , Brazil

Novartis Investigative Site

São José do Rio Preto, , Brazil

Novartis Investigative Site

Plovdiv, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Sofia, , Bulgaria

Novartis Investigative Site

Cambridge, Ontario, Canada

Novartis Investigative Site

Valledupar, Cesar Department, Colombia

Novartis Investigative Site

Ibagué, Tolima Department, Colombia

Novartis Investigative Site

Bogotá, , Colombia

Novartis Investigative Site

Bogotá, , Colombia

Novartis Investigative Site

Montería, , Colombia

Novartis Investigative Site

San José, , Costa Rica

Novartis Investigative Site

Brno, Czech Republic, Czechia

Novartis Investigative Site

Prague, , Czechia

Novartis Investigative Site

Helsinki, , Finland

Novartis Investigative Site

Tampere, , Finland

Novartis Investigative Site

Besançon, , France

Novartis Investigative Site

Caen, , France

Novartis Investigative Site

Clermont-Ferrand, , France

Novartis Investigative Site

Lyon 08, , France

Novartis Investigative Site

Marseille, , France

Novartis Investigative Site

Montpellier, , France

Novartis Investigative Site

Saint-Herblain, , France

Novartis Investigative Site

Strasbourg, , France

Novartis Investigative Site

Valenciennes, , France

Novartis Investigative Site

Langen, Hesse, Germany

Novartis Investigative Site

Augsburg, , Germany

Novartis Investigative Site

Berlin, , Germany

Novartis Investigative Site

Bonn, , Germany

Novartis Investigative Site

Dresden, , Germany

Novartis Investigative Site

Dresden, , Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Tübingen, , Germany

Novartis Investigative Site

Weiden, , Germany

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Debrecen, , Hungary

Novartis Investigative Site

Szolnok, , Hungary

Novartis Investigative Site

Raipur, Chhattisgarh, India

Novartis Investigative Site

Nagpur, Maharashtra, India

Novartis Investigative Site

Bhubaneshwar, Odisha, India

Novartis Investigative Site

Delhii, , India

Novartis Investigative Site

Mumbai, , India

Novartis Investigative Site

Amman, , Jordan

Novartis Investigative Site

Kaunas, LTU, Lithuania

Novartis Investigative Site

Vilnius, , Lithuania

Novartis Investigative Site

Trujillo, La Libertad, Peru

Novartis Investigative Site

San Borja, Lima region, Peru

Novartis Investigative Site

San Isidro, Lima region, Peru

Novartis Investigative Site

San Miguel, Lima region, Peru

Novartis Investigative Site

Lisbon, , Portugal

Novartis Investigative Site

Loures, , Portugal

Novartis Investigative Site

Porto, , Portugal

Novartis Investigative Site

Arkhangelsk, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Saint Petersburg, , Russia

Novartis Investigative Site

Cape Town, , South Africa

Novartis Investigative Site

Johannesburg, , South Africa

Novartis Investigative Site

Parktown, , South Africa

Novartis Investigative Site

Stockholm, , Sweden

Novartis Investigative Site

Stockholm, , Sweden

Novartis Investigative Site

Uppsala, , Sweden

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Chiang Mai, , Thailand

Countries

United States; Argentina; Austria; Belgium; Brazil; Bulgaria; Canada; Colombia; Costa Rica; Czechia; Finland; France; Germany; Hungary; India; Jordan; Lithuania; Peru; Portugal; Russia; South Africa; Sweden; Thailand

References

Cardoso F, Jacot W, Kuemmel S, Gupta S, Cruz F, Balaraman R, Ferreira A, Ahola T, Chapko Y, Zhukova L, Chiang W, Li Z, Ji Y, Kaakiou N, Bolotova N, Sparano JA. 600- vs 400-mg First-Line Ribociclib in Hormone Receptor-Positive/ERBB2-Negative Advanced Breast Cancer: The AMALEE Randomized Clinical Trial. JAMA Oncol. 2025 Sep 25:e253687. doi: 10.1001/jamaoncol.2025.3687. Online ahead of print.

Reference Type: DERIVED

PMID: 40996770 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2786

A Plain Language Trial Summary is available on www.novctrd.com

Other Identifiers

2018-004234-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLEE011A2207

Identifier Type: -

Identifier Source: org_study_id