Breast Cancer Clinical Trial
— AMALEEOfficial 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
Verified date | April 2024 |
Source | Novartis |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Novartis Pharmaceuticals |
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,
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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