Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2010-018782-32 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a first-in-man trial, in which BYL719 will be administered to adult patients with advanced solid tumors, whose tumors have an alteration of the PIK3CA gene and whose disease has progressed despite standard therapy or for whom no standard therapy exists. A combination of BYL719 with fulvestrant will also be investigated in post-menopausal patients with locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene. The single agent MTD dose expansion cohort and the fulvestrant combination MTD dose expansion cohort will also include ER+/HER2- breast cancer patients whose tumors have the wild type PIK3CA gene
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BYL719 | Experimental | In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene |
|
| BYL719 + fulvestrant | Experimental | In post-menopausal patients with estrogen receptor positive locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BYL719 | Drug | BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence rate of dose limiting toxicities (DLT). | MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant. | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Overall safety and tolerability of BYL719 as single agent and in combination with fulvestrant | Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0. | 10 years |
| PK parameters of BYL719 as single agent and in combination with fulvestrant - AUC-tlast and AUC0-inf. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Medical Center | San Francisco | California | 94143 | United States | ||
| Massachusetts General Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38439079 | Derived | Rodon J, Demanse D, Rugo HS, Burris HA, Simo R, Farooki A, Wellons MF, Andre F, Hu H, Vuina D, Quadt C, Juric D. A risk analysis of alpelisib-induced hyperglycemia in patients with advanced solid tumors and breast cancer. Breast Cancer Res. 2024 Mar 4;26(1):36. doi: 10.1186/s13058-024-01773-1. | |
| 30543347 | Derived |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Fulvestrant |
| Drug |
In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene. Fulvestrant is an estrogen receptor antagonist, administered by monthly intramuscular injection |
|
PK parameters AUC-tlast and AUC0-inf |
| 5 years |
| PK parameters of BYL719 as single agent and in combination with fulvestrant - Cmax. | PK parameter Cmax | 5 years |
| Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Tmax. | PK parameter Tmax | 5 years |
| Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - CL/F. | PK parameter CL/F | 5 years |
| Pharmaconkinetics of BYL719 as single agent and in combination with fulvestrant - Vz/F. | PK parameter Vz/F | 5 years |
| Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Terminal half-life (t1/2) | PK parameter t1/2 | 5 years |
| Preliminary efficacy of BYL719 as single agent and in combination with fulvestrant by measuring ORR. | Objective tumor response rate (ORR), defined as the sum of complete response and partial response as best reported response by RECIST 1.0 criteria (Novartis v2.0 guideline) | 5 years |
| Progression-free survival at maximum tolerated dose | PFS at MTD | 5 years |
| Boston |
| Massachusetts |
| 02114 |
| United States |
| Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4) | Nashville | Tennessee | 37203 | United States |
| Vanderbilt Univeristy SC | Nashville | Tennessee | 37232 | United States |
| MD Anderson Cancer Center/University of Texas MD Anderson | Houston | Texas | 77030-4009 | United States |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Würzburg | 97080 | Germany |
| Novartis Investigative Site | Amsterdam | 1066 CX | Netherlands |
| Novartis Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| Novartis Investigative Site | L'Hospitalet de Llobregat | Catalonia | 08907 | Spain |
| Novartis Investigative Site | Oxford | OX3 7LJ | United Kingdom |
| Juric D, Janku F, Rodon J, Burris HA, Mayer IA, Schuler M, Seggewiss-Bernhardt R, Gil-Martin M, Middleton MR, Baselga J, Bootle D, Demanse D, Blumenstein L, Schumacher K, Huang A, Quadt C, Rugo HS. Alpelisib Plus Fulvestrant in PIK3CA-Altered and PIK3CA-Wild-Type Estrogen Receptor-Positive Advanced Breast Cancer: A Phase 1b Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):e184475. doi: 10.1001/jamaoncol.2018.4475. Epub 2019 Feb 14. |
| 29401002 | Derived | Juric D, Rodon J, Tabernero J, Janku F, Burris HA, Schellens JHM, Middleton MR, Berlin J, Schuler M, Gil-Martin M, Rugo HS, Seggewiss-Bernhardt R, Huang A, Bootle D, Demanse D, Blumenstein L, Coughlin C, Quadt C, Baselga J. Phosphatidylinositol 3-Kinase alpha-Selective Inhibition With Alpelisib (BYL719) in PIK3CA-Altered Solid Tumors: Results From the First-in-Human Study. J Clin Oncol. 2018 May 1;36(13):1291-1299. doi: 10.1200/JCO.2017.72.7107. Epub 2018 Feb 5. |
| 25002028 | Derived | Vora SR, Juric D, Kim N, Mino-Kenudson M, Huynh T, Costa C, Lockerman EL, Pollack SF, Liu M, Li X, Lehar J, Wiesmann M, Wartmann M, Chen Y, Cao ZA, Pinzon-Ortiz M, Kim S, Schlegel R, Huang A, Engelman JA. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors. Cancer Cell. 2014 Jul 14;26(1):136-49. doi: 10.1016/j.ccr.2014.05.020. Epub 2014 Jul 4. |
| ID | Term |
|---|---|
| C585539 | Alpelisib |
| D000077267 | Fulvestrant |
| ID | Term |
|---|---|
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
Not provided
Not provided