Phase 1b Trial of BGJ398/BYL719 in Solid Tumors
- Conditions
- Advanced Solid TumorsMetastatic Solid Tumors
- Interventions
- Registration Number
- NCT01928459
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
To study the safety and efficacy of the combination of BGJ398 with BYL719 in patients whose tumors express mutations to PIK3CA with or without alterations to FGFR 1-3.
- Detailed Description
This dose escalation/dose expansion study will evaluate the combination of orally administered BGJ398 in combination with orally administered BYL719. During the dose escalation part, the MTD of the combination will be determined in patients whose advanced or metastatic tumors express mutations to PIK3CA. Once the MTD has been determined, the expansion part will begin. Patients will be addd to one of three arms based on the disease type and genetic changes. Patients with metastatic colorectal cancer are not eligible for participation in the expansion part.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
- Histologically/cytologically confirmed advanced or metastatic solid tumors who have failed standard therapy or for whom no effective standard anti-cancer therapy exists
- Documented PIK3CA mutations in all patients in dose escalation and expansion with or without documented genetic alterations in FGFR depending upon dose expansion cohort (either local or central determination)
- Measurable disease defined by RECIST v1.1
- ECOG performance status of ≤2
- Prior PI3Ki or selective FGFR inhibitor treatment (for patients enrolled to expansion part)
- Colorectal cancer (for patients enrolled to expansion part)
- Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting glucose ≥ 140 mg/dL / 7.8 mmol/L, history of clinically significant gestational diabetes mellitus or documented steroid-induced diabetes mellitus
- Use of medications that increase serum levels of phosphorus and/or calcium
- Inorganic phosphorus outside of normal limits
- Total and ionized serum calcium outside of normal limits
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Solid tumor arm 1 BGJ398 Patients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA. Solid tumor arm 2 BGJ398 Patients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3 Dose escalation BYL719 To determine the MTD or RDE of the combination of BGJ398 with BYL719 in patients with advanced or metastastic solid tumors that express mutations to PIK3CA. Solid tumor arm 2 BYL719 Patients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3 Metastatic breast cancer BGJ398 Evaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3. Metastatic breast cancer BYL719 Evaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3. Solid tumor arm 1 BYL719 Patients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA. Dose escalation BGJ398 To determine the MTD or RDE of the combination of BGJ398 with BYL719 in patients with advanced or metastastic solid tumors that express mutations to PIK3CA.
- Primary Outcome Measures
Name Time Method Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719 Approximately 8 months The dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or the recommended dose for expansion (RDE). Safety(incidence and nature of DLTs), pharmacokinetic and pharmacodynamic data will guide dose escalation decisioins.
- Secondary Outcome Measures
Name Time Method Progression free survival Every two months from the date of baseline CT scan Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719
Overall response rate Every two months from the date of baseline CT scan Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719; Overall response rate = complete response + partial response
Time vs. concentration profile of BGJ398 and BYL719 Every 28 days for up to 10 cycles Plasma concentration versus time profiles. Plasma PK parameters will be used to characterize the PK profiles of the combination of BGJ398 with BYL719
Safety and tolerability of BGJ398/BYL719 combination at the recommended dose for expansion (RDE) Every 28 days from baseline visit until end of study visit This will be assessed by looking at the number of Adverse Events (AEs), serious AEs (SAEs) changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions and reductions
Trial Locations
- Locations (8)
H. Lee Moffitt Cancer Center & Research Institute Moffitt 4
🇺🇸Tampa, Florida, United States
University of Michigan Comprehensive Cancer Center SC
🇺🇸Ann Arbor, Michigan, United States
Karmanos Cancer Institute Dept of Onc
🇺🇸Detroit, Michigan, United States
Washington University School of Medicine Onc Dept
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center Onc Dept
🇺🇸New York, New York, United States
Cancer Therapy & Research Center / UT Health Science Center SC
🇺🇸San Antonio, Texas, United States
Vanderbilt University Medical Center Dept of Onc
🇺🇸Nashville, Tennessee, United States
Novartis Investigative Site
🇨🇭Bellinzona, Switzerland