Clinical trial NCT01928459: Phase 1b Trial of BGJ398/BYL719 in Solid Tumors
Official title: A Phase Ib, Open-label Study of Oral BGJ398 in Combination With Oral BYL719 in Adult Patients With Select Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Metastatic Solid Tumors
Keywords: BGJ398
BYL719
advanced solid tumor
metastatic breast cancer
PK3CA
FGFR
fibroblast growth factor receptor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-08-26
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719
timeFrame: Approximately 8 months
Secondary outcomes:
measure: Safety and tolerability of BGJ398/BYL719 combination at the recommended dose for expansion (RDE)
timeFrame: Every 28 days from baseline visit until end of study visit
measure: Overall response rate
timeFrame: Every two months from the date of baseline CT scan
measure: Progression free survival
timeFrame: Every two months from the date of baseline CT scan
measure: Time vs. concentration profile of BGJ398 and BYL719
timeFrame: Every 28 days for up to 10 cycles
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute Moffitt 4
state: Florida
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center SC
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute Dept of Onc
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine Onc Dept
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Onc Dept
state: New York
city: Nashville
country: United States
facility: Vanderbilt University Medical Center Dept of Onc
state: Tennessee
city: San Antonio
country: United States
facility: Cancer Therapy & Research Center / UT Health Science Center SC
state: Texas
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Saint Herblain cedex
country: France
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Bellinzona
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: