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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03822468
Other study ID # CLEE011A2207
Secondary ID 2018-004234-15
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date June 11, 2019
Est. completion date July 1, 2024

Study information

Verified date April 2024
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

QT interval prolongation and neutropenia are considered to be important identified risks for ribociclib. 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 a non-steroidal aromatase inhibitor (NSAI) in pre- and postmenopausal women with hormone receptor-positive (HR-positive), HER2-negative advanced breast cancer (aBC) who have not received prior therapy for advanced disease.


Description:

This is a phase II, multicenter, randomized, open-label study to evaluate the safety and efficacy of a reduced ribociclib dose of 400 mg in combination with an NSAI (letrozole or anastrozole) for the treatment of pre- and postmenopausal women with HR-positive, HER2-negative aBC who have received no prior therapy for advanced disease. Patients will be randomly assigned to one of the below treatment arms in a 1:1 ratio: - Experimental arm - Ribociclib 400 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women) - Control arm - Ribociclib 600 mg QD 3 weeks on/1 week off + NSAI (+ goserelin in premenopausal women). Participants will receive 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. Continuation of study treatment beyond initial disease progression (RECIST 1.1) will not be allowed. For participants who discontinue treatment for reasons other than documented disease progression, death, lost to follow-up, or withdrawal of consent, tumor assessments must continue to be performed until disease progression, death, lost to follow-up, or withdrawal of consent (post-treatment efficacy follow-up).


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 376
Est. completion date July 1, 2024
Est. primary completion date June 11, 2021
Accepts healthy volunteers No
Gender Female
Age group 18 Years and older
Eligibility 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: - 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 ß-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). 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
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 is supplied as 200 mg tablets as individual patient supply packaged bottles.
Anastrozole
Anastrozole 1 mg tablets for oral use QD continuously
Letrozole
Letrozole 2.5 mg tablets for oral use QD continuously
Goserelin
Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

Locations

Country Name City State
Argentina Novartis Investigative Site San Juan
Austria Novartis Investigative Site Innsbruck
Austria Novartis Investigative Site Linz
Austria Novartis Investigative Site Salzburg
Austria Novartis Investigative Site Vienna
Belgium Novartis Investigative Site Edegem Antwerpen
Belgium Novartis Investigative Site Namur
Brazil Novartis Investigative Site Florianopolis Santa Catarina
Brazil Novartis Investigative Site Goiania GO
Brazil Novartis Investigative Site Natal RN
Brazil Novartis Investigative Site Sao Jose do Rio Preto
Brazil Novartis Investigative Site Sao Paulo SP
Brazil Novartis Investigative Site Sao Paulo SP
Bulgaria Novartis Investigative Site Plovdiv
Bulgaria Novartis Investigative Site Sofia
Bulgaria Novartis Investigative Site Sofia
Canada Novartis Investigative Site Cambridge Ontario
Colombia Novartis Investigative Site Bogota
Colombia Novartis Investigative Site Bogota
Colombia Novartis Investigative Site Ibague Tolima
Colombia Novartis Investigative Site Monteria
Colombia Novartis Investigative Site Valledupar Cesar
Costa Rica Novartis Investigative Site San Jose
Czechia Novartis Investigative Site Brno Czech Republic
Czechia Novartis Investigative Site Praha 5
Finland Novartis Investigative Site Helsinki
Finland Novartis Investigative Site Tampere
France Novartis Investigative Site Besancon Cedex
France Novartis Investigative Site Caen
France Novartis Investigative Site Clermont Ferrand
France Novartis Investigative Site Lyon Cedex 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
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 Langen Hessen
Germany Novartis Investigative Site Tuebingen
Germany Novartis Investigative Site Weiden
Hungary Novartis Investigative Site Budapest
Hungary Novartis Investigative Site Debrecen
Hungary Novartis Investigative Site Szolnok
India Novartis Investigative Site Bhubaneshwar Orissa
India Novartis Investigative Site Delhii
India Novartis Investigative Site Mumbai
India Novartis Investigative Site Nagpur Maharashtra
India Novartis Investigative Site Raipur Chhattisgarh
Jordan Novartis Investigative Site Amman
Lithuania Novartis Investigative Site Kaunas LTU
Lithuania Novartis Investigative Site Vilnius
Peru Novartis Investigative Site San Borja Lima
Peru Novartis Investigative Site San Isidro Lima
Peru Novartis Investigative Site San Miguel Lima
Peru Novartis Investigative Site Trujillo La Libertad
Portugal Novartis Investigative Site Lisbon
Portugal Novartis Investigative Site Loures
Portugal Novartis Investigative Site Porto
Russian Federation Novartis Investigative Site Arkhangelsk
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site St Petersburg
Russian Federation Novartis Investigative Site St Petersburg
South Africa Novartis Investigative Site Cape Town
South Africa Novartis Investigative Site Johannesburg
South Africa Novartis Investigative Site Parktown
Sweden Novartis Investigative Site Stockholm
Sweden Novartis Investigative Site Stockholm
Sweden Novartis Investigative Site Uppsala
Thailand Novartis Investigative Site Bangkok
Thailand Novartis Investigative Site Chiang Mai
United States New York Oncology Hematology SC Albany New York
United States Weinberg Cancer Institute at Franklin Square Hospital Baltimore Maryland
United States Montefiore Medical Center Bronx New York
United States Marin Cancer Care Greenbrae California
United States Comprehensive Cancer Centers of Nevada CCC of Nevada Henderson (4) Henderson Nevada
United States Millennium Research Clin Develop . Houston Texas
United States Nebraska Hematology-Oncology, P.C. Lincoln Nebraska
United States Rocky Mountain Cancer Centers Rocky Mountain Cancer Ctr (50) Longmont Colorado
United States Texas Oncology McAllen Texas
United States Southern Cancer Center PC . Mobile Alabama
United States Mount Sinai School of Medicine CFTY720D2306 New York New York
United States Nebraska Cancer Specialists Oncology Hematology West Omaha Nebraska
United States Florida Retina Institute Orlando Florida
United States Northwest Medical Specialties Dept.ofNW Med. Specialties Tacoma Washington

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary 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.
Up to 23.8 months
Secondary 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 (?QTcF). Baseline and Cycle 1 Day 15 at 2 hours post-dose. Cycle = 28 days
Secondary Progression-free Survival (PFS) PFS was defined as the period starting from the date of randomization to the date of the first documented progression or death caused by any reason. PFS will be assessed via a local radiology assessment as well as BIRC according to RECIST 1.1. Up to approximately 60 months
Secondary Clinical Benefit Rate (CBR) CBR is defined as the percentage of participants 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 are defined as per local review as well as BIRC 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.
SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Up to approximately 60 months
Secondary Time to Response (TTR) TTR defined as defined as the time from the date of randomization to the first documented response of either CR or PR. CR and PR are 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.
Up to approximately 60 months
Secondary Duration of Response (DOR) DOR defined as the time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer.
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.
Up to approximately 60 months
Secondary 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. Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
Secondary 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. Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
Secondary 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 Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
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