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

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

ClinicalTrials.gov Identifier: NCT03822468

Novartis Reference Number: CLEE011A2207

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

QT interval prolongation and neutropenia are considered to be important identified risks for ribociclib (Kisqali® Prescribing Information, Investigator Brochure). The approved dosing regimen of ribociclib is 600 mg daily (QD) on a 3 weeks on/1 week off schedule.

The purpose of the study is to explore whether a reduced dosing regimen of 400 mg ribociclib orally QD 3 weeks on/1 week off may decrease the risk of QTc prolongation without compromising the efficacy of ribociclib in combination with an NSAI in pre- and postmenopausal women with HR-positive, HER2-negative aBC who have received no prior therapy for advanced disease. The risks of other AEs of special interest, such as neutropenia and hepatobiliary toxicity will be evaluated in this study as well.

Approximately 350 patients will be randomly assigned to one of the below treatment arms in a 1:1 ratio: Experimental arm (Arm 1) - Ribociclib 400 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Control arm (Arm 2) - Ribociclib 600 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women): 175 patients Randomization will be stratified by the presence of lung and/or liver metastases (yes versus no).

Condition 
Breast Cancer
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
350 participants
Start date 
Jun 11, 2019
Completion date 
Feb 02, 2026
Gender 
Female
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Ribociclib
Ribociclib will be supplied as 200 mg tablets as individual patient supply packaged bottles taken by mouth.
Drug
Letrozole or Anastrozole
Letrozole 2.5 mg by mouth QD continuously or anastrozole 1 mg by mouth QD continuously (investigator choice)
Drug
Goserelin
Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

Eligibility Criteria

Key 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:

QTc interval at screening < 450 ms (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.

Key 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).

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.

Study Locations

United States
Southern Cancer Center PC
Recruiting
Mobile, 36608
Alabama
United States
Marin Cancer Care
Recruiting
Greenbrae, 94904
California
United States
Rocky Mountain Cancer Centers Rocky Mountain Cancer Ctr (50)
Recruiting
Greenwood Village, 80111
Colorado
United States
Mid Florida Hematology and Oncology Center
Recruiting
Orange City, 32763
Florida
United States
Florida Retina Institute
Recruiting
Orlando, 32804
Florida
United States
Emory University School of Medicine/Winship Cancer Institute
Recruiting
Atlanta, 30322
Georgia
United States
Weinberg Cancer Institute at Franklin Square Hospital
Recruiting
Baltimore, 21237-3998
Maryland
United States
Nebraska Hematology-Oncology, P.C.
Recruiting
Lincoln, 68506
Nebraska
United States
Nebraska Cancer Specialists Oncology Hematology West
Recruiting
Omaha, 68154
Nebraska
United States
Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)
Recruiting
Las Vegas, 89109
Nevada
United States
New York Oncology Hematology SC
Recruiting
Albany, 12208
New York
United States
Montefiore Medical Center
Recruiting
Bronx, 10467
New York
United States
Mount Sinai School of Medicine CFTY720D2306
Recruiting
New York, 10029
New York
United States
US Oncology Central Monitoring Regulatory - 2
Recruiting
Dallas, 75246
Texas
United States
Millennium Oncology
Recruiting
Houston, 77090
Texas
United States
Texas Oncology
Recruiting
McAllen, 78503
Texas
United States
Tyler Cancer Center
Recruiting
Tyler, 75702
Texas
United States
Community Cancer Trials of Utah
Recruiting
Ogden, 84405
Utah
United States
Northwest Medical Specialties Dept.ofNW Med. Specialties
Recruiting
Tacoma, 98405
Washington
United States
Argentina
Novartis Investigative Site
Recruiting
Caba, C1280AEB
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
San Juan, J5402DIL
-
Argentina
Austria
Novartis Investigative Site
Recruiting
Innsbruck, A-6020
-
Austria
Novartis Investigative Site
Recruiting
Linz, 4010
-
Austria
Novartis Investigative Site
Recruiting
Salzburg, 5020
-
Austria
Novartis Investigative Site
Recruiting
Vienna, 1090
-
Austria
Novartis Investigative Site
Recruiting
Wien, A-1130
-
Austria
Belgium
Novartis Investigative Site
Recruiting
Edegem, 2650
Antwerpen
Belgium
Novartis Investigative Site
Recruiting
Bruxelles, 1200
-
Belgium
Novartis Investigative Site
Recruiting
Namur, 5000
-
Belgium
Novartis Investigative Site
Recruiting
Ottignies, 1340
-
Belgium
Brazil
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Recruiting
Goiania, 74605-070
GO
Brazil
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Recruiting
Natal, 59075 740
RN
Brazil
Novartis Investigative Site
Recruiting
Florianopolis, 88034 000
Santa Catarina
Brazil
Novartis Investigative Site
Recruiting
Sao Paulo, 01317 000
SP
Brazil
Novartis Investigative Site
Active, not recruiting
Sao Paulo, 03102-002
SP
Brazil
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Recruiting
Sao Jose do Rio Preto, 15090 000
-
Brazil
Bulgaria
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Recruiting
Plovdiv, 4004
-
Bulgaria
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Recruiting
Sofia, 1303
-
Bulgaria
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Recruiting
Sofia, 1756
-
Bulgaria
Canada
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Recruiting
Cambridge, N1R 3G2
Ontario
Canada
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Sudbury, P3E 5J1
Ontario
Canada
Colombia
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Recruiting
Valledupar, 5602310
Cesar
Colombia
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Recruiting
Ibague, 730006
Tolima
Colombia
Novartis Investigative Site
Recruiting
Bogota, 110221
-
Colombia
Novartis Investigative Site
Recruiting
Bogota,
-
Colombia
Novartis Investigative Site
Recruiting
Monteria, 230002
-
Colombia
Costa Rica
Novartis Investigative Site
Recruiting
San Jose,
-
Costa Rica
Czechia
Novartis Investigative Site
Recruiting
Brno, 656 53
Czech Republic
Czechia
Novartis Investigative Site
Recruiting
Praha 5, 150 06
-
Czechia
Finland
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Helsinki, 00029
-
Finland
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Tampere, FIN-33521
-
Finland
France
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Besancon Cedex, 25030
-
France
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Caen Cedex, 14021
-
France
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Clermont-Ferrand, 63011
-
France
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Lyon Cedex 08, 69373
-
France
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Recruiting
Marseille, 13273
-
France
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Recruiting
Montpellier Cedex 5, 34298
-
France
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Recruiting
Saint Herblain cedex, 44805
-
France
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Recruiting
Strasbourg, F 67085
-
France
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Recruiting
Valenciennes, 59300
-
France
Germany
Novartis Investigative Site
Recruiting
Muenchen, 80637
Bavaria
Germany
Novartis Investigative Site
Recruiting
Langen, 63225
Hessen
Germany
Novartis Investigative Site
Recruiting
Velbert, 42551
Nordhein-Westfalen
Germany
Novartis Investigative Site
Recruiting
Luebeck, 23563
Schleswig-holstein
Germany
Novartis Investigative Site
Recruiting
Augsburg, 86150
-
Germany
Novartis Investigative Site
Recruiting
Berlin, 13581
-
Germany
Novartis Investigative Site
Recruiting
Bonn, 53111
-
Germany
Novartis Investigative Site
Recruiting
Dresden, 01127
-
Germany
Novartis Investigative Site
Recruiting
Dresden, 01307
-
Germany
Novartis Investigative Site
Recruiting
Essen, 45136
-
Germany
Novartis Investigative Site
Recruiting
Tübingen, 72076
-
Germany
Novartis Investigative Site
Recruiting
Weiden, 92637
-
Germany
Hungary
Novartis Investigative Site
Recruiting
Budapest, H 1122
-
Hungary
Novartis Investigative Site
Recruiting
Debrecen, 4032
-
Hungary
Novartis Investigative Site
Recruiting
Szolnok, H-5000
-
Hungary
India
Novartis Investigative Site
Recruiting
Tamil Nadu, 600035
Chennai
India
Novartis Investigative Site
Recruiting
Raipur, 492001
Chhattisgarh
India
Novartis Investigative Site
Recruiting
Nagpur, 441108
Maharashtra
India
Novartis Investigative Site
Recruiting
Bhubaneshwar, 751007
Orissa
India
Novartis Investigative Site
Recruiting
Jaipur, 302017
Rajasthan
India
Novartis Investigative Site
Recruiting
Delhii, 110 085
-
India
Novartis Investigative Site
Recruiting
Mumbai, 400 012
-
India
Jordan
Novartis Investigative Site
Recruiting
Amman, 11941
-
Jordan
Lithuania
Novartis Investigative Site
Recruiting
Kaunas, LT 50161
LTU
Lithuania
Novartis Investigative Site
Recruiting
Vilnius, LT-08660
-
Lithuania
Peru
Novartis Investigative Site
Recruiting
Trujillo,
La Libertad
Peru
Novartis Investigative Site
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San Borja, 41
Lima
Peru
Novartis Investigative Site
Recruiting
San Isidro, 27
Lima
Peru
Novartis Investigative Site
Recruiting
San Miguel, 32
Lima
Peru
Novartis Investigative Site
Recruiting
Arequipa,
-
Peru
Portugal
Novartis Investigative Site
Recruiting
Lisbon, 1400 038
-
Portugal
Novartis Investigative Site
Recruiting
Loures, 2674514
-
Portugal
Novartis Investigative Site
Recruiting
Porto, 4200-072
-
Portugal
Russian Federation
Novartis Investigative Site
Recruiting
Arkhangelsk, 163045
-
Russian Federation
Novartis Investigative Site
Recruiting
Moscow, 111123
-
Russian Federation
Novartis Investigative Site
Recruiting
Moscow, 115478
-
Russian Federation
Novartis Investigative Site
Recruiting
St Petersburg, 197758
-
Russian Federation
Novartis Investigative Site
Recruiting
St-Petersburg, 189646
-
Russian Federation
South Africa
Novartis Investigative Site
Recruiting
Cape Town, 7500
-
South Africa
Novartis Investigative Site
Recruiting
Johannesburg, 2196
-
South Africa
Novartis Investigative Site
Recruiting
Parktown, 2193
-
South Africa
Novartis Investigative Site
Recruiting
Pretoria,
-
South Africa
Sweden
Novartis Investigative Site
Recruiting
Stockholm, 112 19
-
Sweden
Novartis Investigative Site
Recruiting
Stockholm, SE-118 83
-
Sweden
Novartis Investigative Site
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Uppsala, 751 85
-
Sweden
Novartis Investigative Site
Recruiting
Vaxjo, SE-351 85
-
Sweden
Thailand
Novartis Investigative Site
Recruiting
Bangkok, 10700
-
Thailand
Novartis Investigative Site
Recruiting
Chiang Mai, 50200
-
Thailand

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111

Have a question?

Call 1-999-669-6682 or email [email protected]