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Breast CancerPhase 2AMALEENCT03822468

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

A Phase 2 study testing Ribociclib, Anastrozole and Letrozole in people with Breast Cancer, run by Novartis Pharmaceuticals at 89 sites in 23 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 100 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
Ribociclib, Anastrozole and Letrozole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
376 participants
Where
89 sitesin 23 countries
Study dates
11 Jun 2019to 30 Aug 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

89 sites in 23 countries.

89 sites in 23 countries

United States14 sites

  • New York Oncology Hematology

    Albany, New York, 12208

  • Weinberg Cancer Institute at FSH

    Baltimore, Maryland, 21237-3998

  • Marin Cancer Care

    Greenbrae, California, 94904

  • Comprehensive Cancer Cntr Of Nevada

    Henderson, Nevada, 89052

  • Millennium Research Clin Develop

    Houston, Texas, 77090

  • Nebraska Hematology Oncology P C

    Lincoln, Nebraska, 68506

  • Rocky Mountain Cancer Centers

    Longmont, Colorado, 80501

  • Texas Oncology

    McAllen, Texas, 78503

  • Southern Cancer Center PC

    Mobile, Alabama, 36608

  • Mount Sinai School Of Medicine

    New York, New York, 10029

  • Nebraska Cancer Specialists

    Omaha, Nebraska, 68154

  • Florida Retina Institute

    Orlando, Florida, 32804

  • Northwest Medical Specialties

    Tacoma, Washington, 98405

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

France9 sites

  • Novartis Investigative Site

    Besançon, 25030

  • Novartis Investigative Site

    Caen, 14021

  • Novartis Investigative Site

    Clermont-Ferrand, 63011

  • Novartis Investigative Site

    Lyon 08, 69373

  • Novartis Investigative Site

    Marseille, 13273

  • Novartis Investigative Site

    Montpellier, 34298

  • Novartis Investigative Site

    Saint-Herblain, 44805

  • Novartis Investigative Site

    Strasbourg, F 67085

  • Novartis Investigative Site

    Valenciennes, 59300

Other trials in France

Germany9 sites

  • Novartis Investigative Site

    Augsburg, 86150

  • Novartis Investigative Site

    Berlin, 13581

  • Novartis Investigative Site

    Bonn, 53111

  • Novartis Investigative Site

    Dresden, 01127

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Essen, 45136

  • Novartis Investigative Site

    Langen, Hesse, 63225

  • Novartis Investigative Site

    Tübingen, 72076

  • Novartis Investigative Site

    Weiden, 92637

Other trials in Germany

Brazil6 sites

  • Novartis Investigative Site

    Florianópolis, Santa Catarina, 88034 000

  • Novartis Investigative Site

    Goiânia, 74605-070

  • Novartis Investigative Site

    Natal, Rio Grande do Norte, 59075 740

  • Novartis Investigative Site

    São José do Rio Preto, 15090 000

  • Novartis Investigative Site

    São Paulo, São Paulo, 01317 000

  • Novartis Investigative Site

    São Paulo, São Paulo, 04014-002

Other trials in Brazil

Colombia5 sites

  • Novartis Investigative Site

    Bogotá, 110131

  • Novartis Investigative Site

    Bogotá, 110221

  • Novartis Investigative Site

    Ibague, Tolima Department, 730006

  • Novartis Investigative Site

    Montería, 230002

  • Novartis Investigative Site

    Valledupar, Cesar Department, 5602310

Other trials in Colombia

India5 sites

  • Novartis Investigative Site

    Bhubaneswar, Odisha, 751007

  • Novartis Investigative Site

    Delhii, 110 085

  • Novartis Investigative Site

    Mumbai, 400 012

  • Novartis Investigative Site

    Nagpur, Maharashtra, 441108

  • Novartis Investigative Site

    Raipur, Chhattisgarh, 492001

Other trials in India

Austria4 sites

  • Novartis Investigative Site

    Innsbruck, Tyrol, 6020

  • Novartis Investigative Site

    Linz, 4010

  • Novartis Investigative Site

    Salzburg, 5020

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

Peru4 sites

  • Novartis Investigative Site

    San Borja, Lima region, 41

  • Novartis Investigative Site

    San Isidro, Lima region, 27

  • Novartis Investigative Site

    San Miguel, Lima region, 32

  • Novartis Investigative Site

    Trujillo, La Libertad, 13011

Other trials in Peru

Russia4 sites

  • Novartis Investigative Site

    Arkhangelsk, 163045

  • Novartis Investigative Site

    Moscow, 111123

  • Novartis Investigative Site

    Moscow, 115478

  • Novartis Investigative Site

    Saint Petersburg, 197758

Other trials in Russia

Bulgaria3 sites

  • Novartis Investigative Site

    Plovdiv, 4004

  • Novartis Investigative Site

    Sofia, 1303

  • Novartis Investigative Site

    Sofia, 1756

Other trials in Bulgaria

Hungary3 sites

  • Novartis Investigative Site

    Budapest, H 1122

  • Novartis Investigative Site

    Debrecen, 4032

  • Novartis Investigative Site

    Szolnok, H-5000

Other trials in Hungary

Portugal3 sites

  • Novartis Investigative Site

    Lisbon, 1400-038

  • Novartis Investigative Site

    Loures, 2674514

  • Novartis Investigative Site

    Porto, 4200-072

Other trials in Portugal

South Africa3 sites

  • Novartis Investigative Site

    Cape Town, 7500

  • Novartis Investigative Site

    Johannesburg, 2196

  • Novartis Investigative Site

    Parktown, 2193

Other trials in South Africa

Sweden3 sites

  • Novartis Investigative Site

    Stockholm, 112 19

  • Novartis Investigative Site

    Stockholm, SE-118 83

  • Novartis Investigative Site

    Uppsala, 751 85

Other trials in Sweden

Belgium2 sites

  • Novartis Investigative Site

    Edegem, 2650

  • Novartis Investigative Site

    Namur, 5000

Other trials in Belgium

Czechia2 sites

  • Novartis Investigative Site

    Brno, Czech Republic, 656 53

  • Novartis Investigative Site

    Prague, 150 06

Other trials in Czechia

Finland2 sites

  • Novartis Investigative Site

    Helsinki, 00029

  • Novartis Investigative Site

    Tampere, FIN-33521

Other trials in Finland

Lithuania2 sites

  • Novartis Investigative Site

    Kaunas, LTU, LT 50161

  • Novartis Investigative Site

    Vilnius, LT-08660

Other trials in Lithuania

Thailand2 sites

  • Novartis Investigative Site

    Bangkok, 10700

  • Novartis Investigative Site

    Chiang Mai, 50200

Other trials in Thailand

Argentina1 site

  • Novartis Investigative Site

    San Juan, J5402DIL

Other trials in Argentina

Canada1 site

  • Novartis Investigative Site

    Cambridge, Ontario, N1R 3G2

Other trials in Canada

Costa Rica1 site

  • Novartis Investigative Site

    San José, 95008

Other trials in Costa Rica

Jordan1 site

  • Novartis Investigative Site

    Amman, 11941

Other trials in Jordan

About this study

Official title: A Phase II, Multicenter, Randomized, Open-label Study to Evaluate the Safety and Efficacy of 400 mg of Ribociclib in Combination With Non-steroidal Aromatase Inhibitors for the Treatment of Pre- and Postmenopausal Women With Hormone Receptor-positive, HER2-negative Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease

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.

Read the 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
Being tested
Ribociclib, Anastrozole, Letrozole, Goserelin
Keywords
Breast Cancer (BC), hormone receptor (HR), HR-positive, human epidermal growth factor receptor 2 (HER2), HER2-negative, ER-positive, advanced breast cancer (aBC), ribociclib (LEE011), premenopausal, postmenopausal
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RibociclibDrug

    Also called LEE011

    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.

  • AnastrozoleDrug

    Anastrozole 1 mg tablets for oral use QD continuously

  • LetrozoleDrug

    Letrozole 2.5 mg tablets for oral use QD continuously

  • GoserelinDrug

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

Study groups in NCT03822468
Study groupRoleWhat they receive
Ribociclib 400 mgExperimentalRibociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
Receives: Drug: Ribociclib; Drug: Anastrozole; Drug: Letrozole; Drug: Goserelin
Ribociclib 600 mgActive comparatorRibociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
Receives: Drug: Ribociclib; Drug: Anastrozole; Drug: Letrozole; Drug: Goserelin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    ORR defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) assessed by local investigators according to RECIST 1.1.

    CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: Up to 23.8 months

Secondary outcomes (8)

  1. Change From Baseline in QTc (With Fridericia's Correction) at Cycle 1 Day 15 (at 2 Hours Post-dose)

    Electrocardiogram (ECG) data was collected via 12-lead digital ECG machines. Change from baseline in the QT interval (a segment of the ECG that reflects the time it takes for the heart to repolarize after each heartbeat) was corrected for heart rate using Fridericia's formula (ΔQTcF).

    Measured: Baseline and Cycle 1 Day 15 at 2 hours post-dose. Cycle = 28 days

  2. Progression-free Survival (PFS)

    Progression free survival (PFS) was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. PFS was censored if no PFS event was observed. The censoring date was the date of the last adequate tumor assessment. Clinical deterioration without objective radiological evidence was not considered as documented disease progression. PFS was assessed via a local radiology assessment as well as Blinded Independent Review Committee (BIRC) according to RECIST 1.1.

    Measured: Up to approximately 60 months

  3. Clinical Benefit Rate (CBR)

    Clinical benefit rate (CBR) was defined as the proportion of patients with a best overall response of complete response (CR), or partial response (PR), or an overall response of stable disease (SD), lasting for at least 24 weeks. CR, PR, and SD were defined as per local review as well as Blinded Independent Review Committee (BIRC) according to RECIST 1.1. A patient was considered to have SD for 24 weeks or longer if a SD response was recorded at 24-1=23 weeks or later from randomization, allowing for the ±1 week visit window for tumor assessments.

    CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.

    Measured: Up to approximately 60 months

  4. Time to Response (TTR)

    Time to response (TTR) was defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which had to be subsequently confirmed (although the date of initial response was used, not the date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1.

    CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: Up to approximately 60 months

  5. Duration of Response (DOR)

    Duration of response (DOR) only applied to patients whose best overall response was complete response (CR) or partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progression or death due to underlying cancer. Patients continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment.

    CR: Disappearance of all lesions with lymph nodes measuring < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

    Measured: Up to approximately 60 months

  6. Pharmacokinetics (PK) of Ribociclib: Maximum Observed Plasma Concentration (Cmax)

    PK parameters were calculated by non-compartmental analysis. Cmax is the maximum observed plasma drug concentration after single dose administration.

    Measured: Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days

  7. PK of Ribociclib: Time to Reach Observed Maximum Concentration (Tmax)

    PK parameters were calculated by non-compartmental analysis. Tmax is the time to reach maximum observed plasma concentration. Actual recorded sampling times were considered for the calculations.

    Measured: Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days

  8. PK of Ribociclib: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24)

    PK parameters were calculated by non-compartmental analysis. AUC0-24 is the area under the plasma concentration-time curve from 0 to 24 hours

    Measured: Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2019
  2. Study start11 Jun 2019
  3. Primary completion11 Jun 2021
  4. Study completion30 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
376 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03822468
Sponsor's protocol ID
CLEE011A2207
Other IDs
2018-004234-15, 2018
Acronym
AMALEE
Status last verified
Oct 2025
First submitted
28 Jan 2019
Last updated
16 Oct 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Publications

  • Ji Y, Wang C, Combes FP, Ho YY, Fasching PA, Untch M, Zarate JP, Crown J. Quantitative Pharmacology Justifying Ribociclib Dose in Early Breast Cancer. Clin Pharmacokinet. 2026 Aug;65(8):1217-1228. doi: 10.1007/s40262-026-01643-3. Epub 2026 Jun 23.

    PubMed 42334791

  • 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 Nov 1;11(11):1356-1363. doi: 10.1001/jamaoncol.2025.3687.

    PubMed 40996770

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ribociclib, Anastrozole and Letrozole in people with Breast Cancer, run by Novartis Pharmaceuticals at 89 sites in 23 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 89 sites in United States, France, Germany, Brazil, Colombia and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to 23.8 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03822468, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.

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