Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBC

Breast Cancer Clinical Trial

— COMPLEEMENT-1  

Official title:

COMPLEEMENT-1: An Open-label, Multicenter, Phase IIIb Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With Hormone Receptor-positive (HR+) HER2-negative (HER2-) Advanced Breast Cancer (aBC) With no Prior Hormonal Therapy for Advanced Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02941926
• Other study ID #: CLEE011A2404
• Secondary ID: 2016-003467-19
• Status: Completed
• Phase: Phase 3
• Start date: November 30, 2016
• Est. completion date: November 9, 2022

Study information

• Verified date: October 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to collect additional safety and efficacy data for the combination of ribociclib + letrozole in men and pre/postmenopausal women with HR+HER2- advanced breast cancer and no prior hormonal treatment for advanced disease..

Description:

This was an open-label, single arm, multi-center Phase IIIb study. The study was composed of 2 phases: Core Phase and Extension Phase. In the Core Phase, safety and efficacy data was collected. The study treatment during the Core Phase was provided until disease progression, death, unacceptable toxicities, physician's decision, subject/guardian's decision, protocol deviation, study termination by sponsor, lost to follow-up, technical problems or up to 18 months after LPFV. In the event that patients were still deriving benefit at the end of the Core phase and ribociclib was not approved or available and reimbursed, patients were transitioned to the Extension Phase and continued to receive study treatment until progression, intolerance, death or physician/patient decision. Only safety and clinical benefit (as assessed by investigator) data was collected in the Extension Phase. During the Extension Phase, if ribociclib became locally approved and reimbursed, patients were to be transitioned to prescription. Patients who completed the Extension Phase and continued to derive clinical benefit from the treatment based on the investigator's evaluation received ribociclib from prescription (if approved and reimbursed), another post-trial access program, or other drug access/support program(s). Canadian sub-study: this sub-study was a multicenter Canadian exploratory correlative sample collection sub-study that aimed to better understand mechanisms of response and resistance to ribociclib in combination with letrozole therapy. This sub-study was available for all Canadian subjects enrolled on the main study and did not alter the planned treatment.

Other known NCT identifiers

• NCT03613220

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3246
• Est. completion date: November 9, 2022
• Est. primary completion date: November 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Male or female advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
• In the case of women, both pre/perimenopausal and postmenopausal patients were allowed to be included in this study; menopausal status was relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.

1. Postmenopausal status was defined either by: I).Prior bilateral oophorectomy OR ii). Age = 60 OR iii). Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range. If patient was taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels would be in post-menopausal range per local normal range (NCCN Guidelines version 2.2017). Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol were needed to ensure menopausal status.

2. Premenopausal status was defined as either: I).Patient had last menstrual period within the last 12 months OR ii). If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range OR iii). In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.

3. Perimenopausal status was define as neither premenopausal nor postmenopausal

• Patient had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
• Patient had 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 was required by local laboratory testing.
• Patient had an Eastern Cooperative Oncology Group (ECOG) performance status =2
• Patient had adequate bone marrow and organ function as defined by ALL of the following

laboratory values (as assessed by local laboratory):

• Absolute neutrophil count = 1.5 × 10^9/L
• Platelets = 100 × 10^9/L
• Hemoglobin = 9.0 g/dL
• Potassium, sodium, calcium corrected for serum albumin and magnesium within normal limits or corrected to within normal limits with supplements before first dose of the study medication
• INR =1.5
• Serum creatinine <1.5 mg/dl or creatinine clearance=50 mL/min
• In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient had liver metastases, ALT and AST should be < 5 × ULN.
• Total serum bilirubin < ULN; or total bilirubin = 3.0 × ULN with direct bilirubin within normal range in patients with well-documented Gilbert's Syndrome
• Patient must have had a 12-lead ECG with ALL of the following parameters at screening:
• QTcF interval at screening <450 msec (using Fridericia's correction)
• Resting heart rate = 50 bpm

Key Exclusion Criteria:

• Patient who received any CDK4/6 inhibitor
• Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease

was permitted. Note:

• Patients who received (neo) adjuvant therapy for breast cancer were eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole the disease free interval had to be greater than 12 months from the completion of treatment until study entry.
• Patients who received = 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial were eligible.
• Any prior (neo) adjuvant anti-cancer therapy or prior chemotherapy for metastatic disease had to be stopped at least 5 half-lives or 7 days, whichever was longer, before study inclusion.
• Patient was concurrently using other anti-cancer therapy.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Ribociclib
Ribociclib was centrally supplied to the investigators and administered orally once a day on days 1-21 of each 28 day cycle at a starting dose of 600 mg daily
• Letrozole
Letrozole was procured locally and administered orally once a day on a continuous daily schedule at a dose of 2.5 mg
• Goserelin
Goserelin was procured locally and administered in men and premenopausal women as an injectable subcutaneous implant administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 3.6 mg (cycle = 28 days)
• Leuprolide
Leuprolide was procured locally and administered in men and premenopausal women as an injectable intramuscular depot administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 7.5 mg (cycle= 28 days)

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	La Rioja
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	San Miguel De Tucuman	Tucuman
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Innsbruck	Tyrol
Austria	Novartis Investigative Site	Leoben
Austria	Novartis Investigative Site	Rankweil
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Antwerp
Belgium	Novartis Investigative Site	Bonheiden
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Brussels
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Kortrijk
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Luxembourg
Belgium	Novartis Investigative Site	Mons
Belgium	Novartis Investigative Site	Namur
Belgium	Novartis Investigative Site	Roeselare
Belgium	Novartis Investigative Site	Sint Niklaas	Oost Vlaanderen
Belgium	Novartis Investigative Site	Verviers
Belgium	Novartis Investigative Site	Wilrijk
Bulgaria	Novartis Investigative Site	Gabrovo
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Barrie	Ontario
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Cambridge	Ontario
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Kelowna	British Columbia
Canada	Novartis Investigative Site	Kingston	Ontario
Canada	Novartis Investigative Site	Kitchener	Ontario
Canada	Novartis Investigative Site	Laval	Quebec
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Newmarket	Ontario
Canada	Novartis Investigative Site	North York	Ontario
Canada	Novartis Investigative Site	Oshawa	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Regina	Saskatchewan
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	Sault Ste Marie	Ontario
Canada	Novartis Investigative Site	Sherbrooke	Quebec
Canada	Novartis Investigative Site	Sudbury	Ontario
Canada	Novartis Investigative Site	Surrey	British Columbia
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Winnipeg	Manitoba
Chile	Novartis Investigative Site	Santiago
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Ceske Budejovice
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Czechia	Novartis Investigative Site	Liberec	Czech Republic
Czechia	Novartis Investigative Site	Olomouc	CZE
Czechia	Novartis Investigative Site	Pardubice
Czechia	Novartis Investigative Site	Prague 5
Czechia	Novartis Investigative Site	Prague 8	Czech Republic
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Praha 10
Czechia	Novartis Investigative Site	Praha 4
Czechia	Novartis Investigative Site	Zlin	Czech Republic
Denmark	Novartis Investigative Site	Copenhagen
Denmark	Novartis Investigative Site	Vejle
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Oulu
Finland	Novartis Investigative Site	Tampere
France	Novartis Investigative Site	Albi
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France	Novartis Investigative Site	Avignon
France	Novartis Investigative Site	Besancon Cedex
France	Novartis Investigative Site	Bobigny Cedex
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Bordeaux Cedex
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France	Novartis Investigative Site	Dijon	Cote D Or
France	Novartis Investigative Site	Le Mans Cedex
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Limoges
France	Novartis Investigative Site	Limoges	Haute Vienne
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Lyon Cedex 08
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Mont de Marsan cedex
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Nancy
France	Novartis Investigative Site	Nantes Cedex
France	Novartis Investigative Site	Nice Cedex 2	Alpes Maritimes
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris 10
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France	Novartis Investigative Site	Pierre Benite
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France	Novartis Investigative Site	Strasbourg
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Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
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Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Brindisi	BR
Italy	Novartis Investigative Site	Candiolo	TO
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Cona	FE
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Italy	Novartis Investigative Site	Cuneo	CN
Italy	Novartis Investigative Site	Fano	PU
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Italy	Novartis Investigative Site	Grosseto	GR
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Italy	Novartis Investigative Site	Livorno	LI
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Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Mirano	VE
Italy	Novartis Investigative Site	Modena	MO
Italy	Novartis Investigative Site	Monserrato	CA
Italy	Novartis Investigative Site	Monza	MB
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Negrar	VR
Italy	Novartis Investigative Site	Novara
Italy	Novartis Investigative Site	Nuoro	NU
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Palermo	PA
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Pisa	PI
Italy	Novartis Investigative Site	Prato	PO
Italy	Novartis Investigative Site	Reggio Calabria	RC
Italy	Novartis Investigative Site	Reggio Emilia	RE
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Salerno	SA
Italy	Novartis Investigative Site	San Giovanni Rotondo	FG
Italy	Novartis Investigative Site	Saronno	VA
Italy	Novartis Investigative Site	Sassari	SS
Italy	Novartis Investigative Site	Savona	SV
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Taormina	ME
Italy	Novartis Investigative Site	Terni	TR
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Trento	TN
Italy	Novartis Investigative Site	Treviglio	BG
Italy	Novartis Investigative Site	Udine	UD
Italy	Novartis Investigative Site	Verona	VR
Italy	Novartis Investigative Site	Viterbo	VT
Jordan	Novartis Investigative Site	Amman
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Saida
Malaysia	Novartis Investigative Site	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Petaling Jaya	Selangor
Malaysia	Novartis Investigative Site	Putrajaya	Wilayah Persekutuan
Malaysia	Novartis Investigative Site	Tanjong Bungah	Penang
Mexico	Novartis Investigative Site	Ciudad de Mexico
Mexico	Novartis Investigative Site	Mexico City
Mexico	Novartis Investigative Site	Monterrey	Nuevo Leon
Netherlands	Novartis Investigative Site	Apeldoorn	DZ
Netherlands	Novartis Investigative Site	Arnhem	Gelderland
Netherlands	Novartis Investigative Site	Beverwijk
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Delft
Netherlands	Novartis Investigative Site	Den Bosch
Netherlands	Novartis Investigative Site	Den Haag
Netherlands	Novartis Investigative Site	Dordrecht
Netherlands	Novartis Investigative Site	Ede
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Enschede
Netherlands	Novartis Investigative Site	Goes
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Hilversum
Netherlands	Novartis Investigative Site	Hoofddorp
Netherlands	Novartis Investigative Site	Leeuwarden
Netherlands	Novartis Investigative Site	Maastricht	AZ
Netherlands	Novartis Investigative Site	Roermond
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Sittard-Geleen
Netherlands	Novartis Investigative Site	Utrecht
Netherlands	Novartis Investigative Site	Venray	CE
Netherlands	Novartis Investigative Site	Zutphen
Netherlands	Novartis Investigative Site	Zwolle
Norway	Novartis Investigative Site	Gralum
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigative Site	Stavanger
Oman	Novartis Investigative Site	Muscat
Panama	Novartis Investigative Site	Panama City
Philippines	Novartis Investigative Site	Las Pinas
Philippines	Novartis Investigative Site	San Juan City
Philippines	Novartis Investigative Site	Taguig City	Metro Manila
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Bytom
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Opole
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Zory	Slaskie
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Guimaraes
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Porto
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Irkutsk
Russian Federation	Novartis Investigative Site	Kaluga
Russian Federation	Novartis Investigative Site	Kazan	Tatarstan Republic
Russian Federation	Novartis Investigative Site	Krasnoyarsk
Russian Federation	Novartis Investigative Site	Leningrad Region	Russia
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow Region Istra Village
Russian Federation	Novartis Investigative Site	Moscow Rerion Balashiha
Russian Federation	Novartis Investigative Site	Rostov-na-Donu
Russian Federation	Novartis Investigative Site	Samara
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Ufa
Russian Federation	Novartis Investigative Site	Yaroslavl
Saudi Arabia	Novartis Investigative Site	Dammam
Saudi Arabia	Novartis Investigative Site	Makkah
Saudi Arabia	Novartis Investigative Site	Riyadh
Saudi Arabia	Novartis Investigative Site	Riyadh
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Banska Bystrica	Slovak Republic
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Poprad
Slovenia	Novartis Investigative Site	Ljubljana
Slovenia	Novartis Investigative Site	Maribor
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Almeria	Andalucia
Spain	Novartis Investigative Site	Badajoz	Extremadura
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona	Cataluna
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	Burgos
Spain	Novartis Investigative Site	Caceres	Extremadura
Spain	Novartis Investigative Site	Castellon	Comunidad Valenciana
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Elche	Alicante
Spain	Novartis Investigative Site	Girona	Catalunya
Spain	Novartis Investigative Site	Granada	Andalucia
Spain	Novartis Investigative Site	Granollers
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Spain	Novartis Investigative Site	Huelva	Andalucia
Spain	Novartis Investigative Site	Jaen	Andalucia
Spain	Novartis Investigative Site	Jerez	Cadiz
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife
Spain	Novartis Investigative Site	Las Palmas De Gran Canarias	Las Palmas De Gran Canaria
Spain	Novartis Investigative Site	Lerida	Cataluna
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Murcia
Spain	Novartis Investigative Site	Palma De Mallorca	Islas Baleares
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Reus	Tarragona
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Toledo	Castilla La Mancha
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Vigo	Pontevedra
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Gothenburg
Sweden	Novartis Investigative Site	Orebro
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Uppsala
Sweden	Novartis Investigative Site	Vaxjo
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Tainan
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Khon Kaen	THA
Thailand	Novartis Investigative Site	Songkhla	Hat Yai
United Kingdom	Novartis Investigative Site	Aberdeen	Scotland
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Cardiff
United Kingdom	Novartis Investigative Site	East Sussex
United Kingdom	Novartis Investigative Site	Edinburgh
United Kingdom	Novartis Investigative Site	Exeter
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Guildford	Surrey
United Kingdom	Novartis Investigative Site	Ipswich	Suffolk
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Maidstone	Kent
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Peterborough	Cambridgeshire
United Kingdom	Novartis Investigative Site	Plymouth
United Kingdom	Novartis Investigative Site	Portsmouth	Hants
United Kingdom	Novartis Investigative Site	Preston
United Kingdom	Novartis Investigative Site	Sheffield
United Kingdom	Novartis Investigative Site	Stoke-on-Trent
United Kingdom	Novartis Investigative Site	Sutton	Surrey
United Kingdom	Novartis Investigative Site	Truro	Cornwall
United Kingdom	Novartis Investigative Site	York	North Yorkshire
United States	New Mexico Cancer Care Alliance .	Albuquerque	New Mexico
United States	Alaska Cancer Research and Education Center	Anchorage	Alaska
United States	Greater Baltimore Medical Center Cancer Center Greater Baltimore Medical Ctr	Baltimore	Maryland
United States	PeaceHealth St Joseph Medical Center	Bellingham	Washington
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	Aultman Cancer Center Main Centre	Canton	Ohio
United States	Ironwood Cancer and Research Centers	Chandler	Arizona
United States	Oncology Speciialists of Charlotte	Charlotte	North Carolina
United States	Cheyenne Regional Medical Center Cheyenne Regional Med Ctr (3)	Cheyenne	Wyoming
United States	Stroger Cook County Hospital Division of Hematology & Onc	Chicago	Illinois
United States	The Christ Hospital Cancer Center Research Program Linder Research Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation Cleveland Clinic (5)	Cleveland	Ohio
United States	University Hospitals of Cleveland Seidman Cancer Center Cleveland Medical Center	Cleveland	Ohio
United States	Florida Cancer Research Institute Dept of Oncology	Davie	Florida
United States	Centura Health Research Center Centura Health Research Center	Denver	Colorado
United States	Trinitas Comprehensive Cancer Center	Elizabeth	New Jersey
United States	Englewood Health	Englewood	New Jersey
United States	Providence Regional Medical Centre of Everett	Everett	Washington
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	McLeod Center for Cancer Treatment and Research	Florence	South Carolina
United States	Poudre Valley Hospital Poudre Valley Health System	Fort Collins	Colorado
United States	Valley View Hospital Cancer Center	Glenwood Springs	Colorado
United States	Indian Univ Health Goshen Center forCancer SC	Goshen	Indiana
United States	Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4)	Henderson	Nevada
United States	Foundation for Sickle Cell Disease Research	Hollywood	Florida
United States	Millennium Research Clin Develop Millennium Oncology - FL	Houston	Texas
United States	Jackson Oncology Associates	Jackson	Mississippi
United States	Joliet Oncology-Hematology Associates Presence Cancer Center	Joliet	Illinois
United States	University of Kansas Medical Center University of Kansas Med Ctr 9	Kansas City	Kansas
United States	Kadlec Clinic Hematology and Onco	Kennewick	Washington
United States	Dayton Physicians	Kettering	Ohio
United States	Clinical Research Alliance	Lake Success	New York
United States	Watson Clinic Center for Research 1730 Location	Lakeland	Florida
United States	Nebraska Hematology-Oncology, P.C.	Lincoln	Nebraska
United States	Pacific Shores Medical Group SC	Long Beach	California
United States	USC Norris Cancer Center	Los Angeles	California
United States	Columbia St Mary s Hospital of Milwaukee St. Mary's Hospital Ozaukee	Milwaukee	Wisconsin
United States	Northwest Oncology	Munster	Indiana
United States	John Ochsner Heart and Vascular Institute Clinical Trials	New Orleans	Louisiana
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Mid Illinois Hematology Oncology Mid Illinois Hema/Onc (3)	Normal	Illinois
United States	Nebraska Cancer Specialists Oncology Hematology West	Omaha	Nebraska
United States	Mid Florida Hematology and Onc Ctr	Orange	Florida
United States	University of California Irvine UC Irvine (11)	Orange	California
United States	Sarah Cannon at Overland Park Regional Medical Center	Overland Park	Kansas
United States	Ventura County Hematology and Oncology	Oxnard	California
United States	The Valley Hospital / Luckow Pavillion	Paramus	New Jersey
United States	Arizona Oncology Associates	Phoenix	Arizona
United States	PCR Oncology	Pismo Beach	California
United States	Northern Light Mercy Hospital SC	Portland	Maine
United States	Oregon Health Sciences University SC-5	Portland	Oregon
United States	Valley Medical Center Research Valley Medical Center	Renton	Washington
United States	Carolina Blood and Cancer Care of South Carolina	Rock Hill	South Carolina
United States	Kaiser Permanente	Rockville	Maryland
United States	Maryland Oncology Hematology P A Columbia	Rockville	Maryland
United States	Mays Cancer Ctr Uthsa Mdacc	San Antonio	Texas
United States	California Pacific Medical Center Onc Dept	San Francisco	California
United States	Summit Cancer Care Summit Cancer Care (SC)	Savannah	Georgia
United States	Virginia Mason Medical Center-Oncology SC	Seattle	Washington
United States	June E. Nylan Cancer Center	Sioux City	Iowa
United States	Somerset Hematology Oncology Associates Somerset Hematolgy Onc -MI	Somerset	New Jersey
United States	Northwest Medical Specialties Dept.ofNW Med. Specialties	Tacoma	Washington
United States	John D Archbold Memorial Hospital John D. Archbold Mem Hosp (4)	Thomasville	Georgia
United States	Alpha Med Physician Group, LLC	Tinley Park	Illinois
United States	Arizona Oncology Associates Arizona Oncology Assoc. (2)	Tucson	Arizona
United States	Oklahoma Cancer Specialists and Research Institute SC-2	Tulsa	Oklahoma
United States	Hope Cancer Center of East Texas	Tyler	Texas
United States	Medical Faculty Assc Inc Medical Faculty Assc., Inc. (2	Washington DC	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Bulgaria,  Canada,  Chile,  Czechia,  Denmark,  Finland,  France,  Greece,  Hong Kong,  Hungary,  India,  Israel,  Italy,  Jordan,  Lebanon,  Malaysia,  Mexico,  Netherlands,  Norway,  Oman,  Panama,  Philippines,  Poland,  Portugal,  Russian Federation,  Saudi Arabia,  Singapore,  Slovakia,  Slovenia,  Spain,  Sweden,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Canadian Sub-study: Proteomic Analysis of Ribociclib and Letrozole Cohort Not Achieving Clinical Benefit Compared to a Cohort Sensitive to Treatment With Ribociclib and Letrozole	Exploratory analysis performed in archival tumor samples collected during screening in the main study. Protein expression levels of the ribociclib plus letrozole cohort that did not achieve clinical benefit (progression within 3 months of treatment) and the cohort sensitive to ribociclib and letrozole (cohort with a time to progression of 22 months or more) were determined using using Single-Pot, Solid-Phase-enhanced, Sample Preparation-Clinical Tissue Proteomics (SP3-CTP). For normalization purposes a pooled internal standard sample, comprised of aliquots of every sample included in the study, was included in each experimental batch. Protein abundances were calculated as the log2 transformed abundances relative to the pooled internal standard. Positive values represent higher protein expression levels compared to the pooled internal standard. Expression levels of proteins that showed association to predicting response to study treatment are presented.	Screening (up to 28 days before first dose of study treatment)
Primary	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment With Ribociclib + Letrozole in the Core Phase	AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s).; SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. A SAE which caused death of the participant was considered as fatal SAE.; AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE.; A participant with multiple severity grades for an AE is only counted under the maximum grade.	From start of treatment up to 30 days after last treatment (for participants who did not enter to the Extension phase) or up to last treatment in the Core phase (for participants who entered the Extension phase), assessed up to approximately 33 months.
Secondary	Time-to-Progression (TTP) Based on Investigator's Assessment (Core Phase)	Time to progression (TTP) is defined as time from date of start of treatment to the date of first documented progression or death due to underlying cancer. Participants with symptoms of rapidly progressing disease without radiologic evidence were classified as progression only when clear evidence of clinical deterioration was documented and/or patient discontinued due to 'Disease progression' or death due to study indication. When there was no documentation of radiologic evidence of progression, and the patient discontinued for 'Disease progression' due to documented clinical deterioration of disease, the date of discontinuation was used as date of progression.; TTP was estimated using the Kaplan-Meier method. 95% CI of median was calculated according to Brookmeyer and Crowley method.	Up to approximately 33 months
Secondary	Overall Response Rate (ORR) Based on Investigator's Assessment (Core Phase)	Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment.; CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 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.; 95% CI was calculated using the exact binomial method.	Up to approximately 33 months
Secondary	Clinical Benefit Rate (CBR) Based on Investigator's Assessment (Core Phase)	Clinical benefit rate (CBR) is defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1 based on investigator's assessment.; CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 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.; 95% CI was calculated using the exact binomial method.	Up to approximately 33 months
Secondary	Change From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Score (Core Phase)	Change from baseline in FACT-B scores was assessed. FACT-B is a self-report instrument that measures multidimensional quality of life (QOL) in patients with breast cancer. The FACT-B consists of 37 questions that address physical, social, emotional, and functional well-being, with specific questions relevant to women with breast cancer. Each item has a score range of 0 (Not at all) to 4 (Very much), with a total score ranging from 0-148. The higher the score, the better the QOL reported by the participant. A positive change from baseline indicates improvement in QoL.; Due to the nature of the questionnaire, only females were asked to complete this questionnaire.	On Day 1 of Cycle 1, 2, 3, 4 ,5, 6, 8, 10, 12 and after that every 3 cycles, and End of treatment, assessed up to 33 months. Cycle=28 days
Secondary	Number of Participants With AEs and SAEs in the Extension Phase	AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s).; SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization.; AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE.; A participant with multiple severity grades for an AE is only counted under the maximum grade.	From first dose of treatment in the Extension phase up to 30 days after last dose of treatment, assessed up approximately 37.6 months
Secondary	Number of Participants With Clinical Benefit (Extension Phase)	Clinical benefit as assessed by the Investigator during Extension phase	On Day 1 of every 3 cycles, starting from Cycle 1 of the Extension phase until end of treatment, assessed up to 37.4 months. Cycle= 28 days