Phase 1b Trial of BGJ398/BYL719 in Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

A Phase Ib, Open-label Study of Oral BGJ398 in Combination With Oral BYL719 in Adult Patients With Select Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01928459
• Other study ID #: CBGJ398X2102
• Status: Completed
• Phase: Phase 1
• Start date: October 2013
• Est. completion date: August 2016

Study information

• Verified date: August 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• BGJ398
BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle.
• BYL719
BYL719 will be administered orally once daily on each day of the 28-day cycle.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Parkville	Victoria
Belgium	Novartis Investigative Site	Bruxelles
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Lyon Cedex
France	Novartis Investigative Site	Saint Herblain cedex
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Modena	MO
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Netherlands	Novartis Investigative Site	Amsterdam
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sevilla	Andalucia
Switzerland	Novartis Investigative Site	Bellinzona
United States	University of Michigan Comprehensive Cancer Center SC	Ann Arbor	Michigan
United States	Karmanos Cancer Institute Dept of Onc	Detroit	Michigan
United States	Vanderbilt University Medical Center Dept of Onc	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center Onc Dept	New York	New York
United States	Washington University School of Medicine Onc Dept	Saint Louis	Missouri
United States	Cancer Therapy & Research Center / UT Health Science Center SC	San Antonio	Texas
United States	H. Lee Moffitt Cancer Center & Research Institute Moffitt 4	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719	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.	Approximately 8 months
Secondary	Safety and tolerability of BGJ398/BYL719 combination at the recommended dose for expansion (RDE)	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	Every 28 days from baseline visit until end of study visit
Secondary	Overall response rate	Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719; Overall response rate = complete response + partial response	Every two months from the date of baseline CT scan
Secondary	Progression free survival	Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719	Every two months from the date of baseline CT scan
Secondary	Time vs. concentration profile of BGJ398 and BYL719	Plasma concentration versus time profiles. Plasma PK parameters will be used to characterize the PK profiles of the combination of BGJ398 with BYL719	Every 28 days for up to 10 cycles

External Links

•   Results for CBGJ398X2102 from the Novartis Clinical Trials website