Clinical Trials List
Protocol NumberCBYL719X2402
NCT Number(ClinicalTrials.gov Identfier)NCT03056755
Completed
2019-07-01 - 2023-05-31
Phase II
Terminated3
ICD-10C50.911
Malignant neoplasm of unspecified site of right female breast
ICD-10C50.912
Malignant neoplasm of unspecified site of left female breast
ICD-10C50.919
Malignant neoplasm of unspecified site of unspecified female breast
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9174.9
Malignant neoplasm of female breast, unspecified
BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
Novartis Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
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Update
2026/03/01
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Completed
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- 陳怡君 無
- 林季宏 無
- MING-YANG WANG 無
- 張端瑩 無
- 羅喬 無
- Wei-Wu Chen 無
The Actual Total Number of Participants Enrolled
0 Completed
Condition/Disease
Advanced Breast Cancer
Objectives
Primary Objective
To assess the proportion of patients who are alive without disease progression at 6 months based on local investigator
assessment per RECIST v1.1 separately in cohorts A and C (alpelisib in combination with fulvestrant) and cohort B
(alpelisib in combination letrozole) among patients with HR+, HER2-negative aBC harboring a PIK3CA mutation
who have progressed on or after prior treatments.
Secondary Objective
To assess PFS based on local investigator assessment for each cohort.
To assess PFS on next-line treatment (PFS2) for each cohort.
To assess overall response rate (ORR) and clinical benefit rate (CBR) based on local investigator assessment for each
cohort.
To assess duration of response (DOR) in patients with confirmed complete response (CR) or PR for each cohort.
To assess Overall Survival (OS) for each cohort
To evaluate he safety and tolerability of the combination for each cohort.
Test Drug
BYL719
Active Ingredient
Alpelisib
Dosage Form
film coated tablet
Dosage
50 & 200
Endpoints
Primary Outcome Measures :
The percentage of patients who are alive without disease progression [ Time Frame: Date of first dose to approximately 6 months in last enrolling cohort ]
Assess the percentage of patients without disease progression based on local investigator assessment per RECIST in cohort A, cohort B and cohort C. Each cohort will be assessed when last patient in each cohort has reached 6 months but final primary assessment will occur upon completion of 6 months of last enrolling cohort
Secondary Outcome Measures :
Progression free survival (PFS) for each cohort [ Time Frame: date of first dose to up to approximately 25 months ]
PFS is defined as the time from the date of first dose of study medication to the date of the first documented progression or death due to any cause occurring in the study. PFS will be assessed based on local investigator's assessment according to RECIST v1.1
Progression free survival (PFS) on next line treatment PFS2) for each cohort [ Time Frame: Date of first dose to date of first documented progression up to approximately 25 months ]
Progression free survival (PFS) on next line treatment (PFS2) is defined as time from the date of first dose of study medication to the date of first documented progression on next-line therapy or death from any cause
Percentage of participants Overall response rate (ORR) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
ORR based on local investigator's assessment according to RECIST v1.1 in each cohort
Percentage of participants with clinical benefit rate (CBR) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
Clinical Benefit Rate (CBR) based on local investigator's assessment according to RECIST v1.1 in each cohort
Duration of response (DOR) [ Time Frame: Date of first documented response to first documented progression or death up to approximately 25 months ]
Duration of Response is the time from the date of first documented response (confirmed CR or PR) to the date of first documented progression or death due to underlying cancer
Percentable of overall suvivial (OS) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
Overall Survival is defined as the time of start of treatment to date of death or lost to follow-up.
The percentage of patients who are alive without disease progression [ Time Frame: Date of first dose to approximately 6 months in last enrolling cohort ]
Assess the percentage of patients without disease progression based on local investigator assessment per RECIST in cohort A, cohort B and cohort C. Each cohort will be assessed when last patient in each cohort has reached 6 months but final primary assessment will occur upon completion of 6 months of last enrolling cohort
Secondary Outcome Measures :
Progression free survival (PFS) for each cohort [ Time Frame: date of first dose to up to approximately 25 months ]
PFS is defined as the time from the date of first dose of study medication to the date of the first documented progression or death due to any cause occurring in the study. PFS will be assessed based on local investigator's assessment according to RECIST v1.1
Progression free survival (PFS) on next line treatment PFS2) for each cohort [ Time Frame: Date of first dose to date of first documented progression up to approximately 25 months ]
Progression free survival (PFS) on next line treatment (PFS2) is defined as time from the date of first dose of study medication to the date of first documented progression on next-line therapy or death from any cause
Percentage of participants Overall response rate (ORR) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
ORR based on local investigator's assessment according to RECIST v1.1 in each cohort
Percentage of participants with clinical benefit rate (CBR) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
Clinical Benefit Rate (CBR) based on local investigator's assessment according to RECIST v1.1 in each cohort
Duration of response (DOR) [ Time Frame: Date of first documented response to first documented progression or death up to approximately 25 months ]
Duration of Response is the time from the date of first documented response (confirmed CR or PR) to the date of first documented progression or death due to underlying cancer
Percentable of overall suvivial (OS) for each cohort [ Time Frame: Date of first dose and up to approximately 25 months ]
Overall Survival is defined as the time of start of treatment to date of death or lost to follow-up.
Inclution Criteria
Inclusion Criteria:
Patient is male or female 18 years or older
Males or females with advanced (locoregionally recurrent or metatstatic) breast cancer not amenable to curative therapy
In case of women, both premenopausal and postmenopausal patients are allowed to be included in study; menopausal status is relevant for the requirement of LHRH agonist (examples for use in this study include but not limited to goserelin, leuprolide or locally available treatment) to be used concomitantly with alpelisib and letrozole/fulvestrant
Patient is postmenopausal woman defined as either:
Prior bilateral oophorectomy or
Age ≥60 or
Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range.
If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.
Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are needed to ensure menopausal status
Patient is premenopausal defined as either:
Patient had last menstrual period within the last 12 months or
If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, or
In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range
Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC
Patient has confirmed HER2-negative advanced breast cancer (aBC)
Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient has a pathology report confirming PIK3CA mutant status by certified laboratory (using validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send tumor tissue to Novartis designated central lab for confirmation of mutational status
Patient must have:
Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior to study entry,
AI treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET(as monotherapy or in combination except CDK 4/6i + AI) as last treatment regimen in cohort C
Maintenance therapies, where applicable, must be regarded as part of the main treatment.
No more than two (2) prior anti-cancer therapies for aBC
Received no more than one prior regimen of chemotherapy in the metastatic setting
Patient has either measurable disease per RECIST v1.1 or at least one predominantly lytic bone lesion must be present
ECOG performance status ≤ 2
Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met)
Patient has adequate bone marrow, coagulation, liver and renal function
Patient is male or female 18 years or older
Males or females with advanced (locoregionally recurrent or metatstatic) breast cancer not amenable to curative therapy
In case of women, both premenopausal and postmenopausal patients are allowed to be included in study; menopausal status is relevant for the requirement of LHRH agonist (examples for use in this study include but not limited to goserelin, leuprolide or locally available treatment) to be used concomitantly with alpelisib and letrozole/fulvestrant
Patient is postmenopausal woman defined as either:
Prior bilateral oophorectomy or
Age ≥60 or
Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range.
If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.
Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are needed to ensure menopausal status
Patient is premenopausal defined as either:
Patient had last menstrual period within the last 12 months or
If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, or
In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range
Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC
Patient has confirmed HER2-negative advanced breast cancer (aBC)
Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient has a pathology report confirming PIK3CA mutant status by certified laboratory (using validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send tumor tissue to Novartis designated central lab for confirmation of mutational status
Patient must have:
Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior to study entry,
AI treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET(as monotherapy or in combination except CDK 4/6i + AI) as last treatment regimen in cohort C
Maintenance therapies, where applicable, must be regarded as part of the main treatment.
No more than two (2) prior anti-cancer therapies for aBC
Received no more than one prior regimen of chemotherapy in the metastatic setting
Patient has either measurable disease per RECIST v1.1 or at least one predominantly lytic bone lesion must be present
ECOG performance status ≤ 2
Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met)
Patient has adequate bone marrow, coagulation, liver and renal function
Exclusion Criteria
Exclusion Criteria:
patient has known hypersensitivity to alpelisib, fulvestrant or letrozole
Patient has received prior treatment with any PI3K inhibitors
Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type II
Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer
Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy
History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (MRI or CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment
Patient with severe liver impairment (Child Pugh score B/C)
Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs
Patient has documented pneumonitis/interstitial lung disease which is active and requiring treatment
Patient has a history of severe cutaneous reactions like Stevens-Johnson-Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necroloysis (TEN) or Drug Reaction with Eosinphilia and Systemic Symptoms (DRESS).
Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must be discontinued prior to day one of study treatment.
Subjects with unresolved osteonecrosis of the jaw.
patient has known hypersensitivity to alpelisib, fulvestrant or letrozole
Patient has received prior treatment with any PI3K inhibitors
Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type II
Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer
Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy
History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis
Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (MRI or CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment
Patient with severe liver impairment (Child Pugh score B/C)
Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs
Patient has documented pneumonitis/interstitial lung disease which is active and requiring treatment
Patient has a history of severe cutaneous reactions like Stevens-Johnson-Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necroloysis (TEN) or Drug Reaction with Eosinphilia and Systemic Symptoms (DRESS).
Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must be discontinued prior to day one of study treatment.
Subjects with unresolved osteonecrosis of the jaw.
The Estimated Number of Participants
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Taiwan
10 participants
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Global
379 participants
