Phase 1b Trial of BGJ398/BYL719 in Solid Tumors

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01928459

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors Metastatic Solid Tumors	Drug: BGJ398 Drug: BYL719	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2013

Actual Primary Completion Date :

Aug 1, 2016

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metastatic breast cancer Evaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3.	Drug: BGJ398 BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle. Drug: BYL719 BYL719 will be administered orally once daily on each day of the 28-day cycle.
Experimental: Solid tumor arm 1 Patients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA.	Drug: BGJ398 BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle. Drug: BYL719 BYL719 will be administered orally once daily on each day of the 28-day cycle.
Experimental: Solid tumor arm 2 Patients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3	Drug: BGJ398 BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle. Drug: BYL719 BYL719 will be administered orally once daily on each day of the 28-day cycle.
Experimental: Dose escalation 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.	Drug: BGJ398 BGJ398 will be administered orally once daily for the first 21 days of each 28-day cycle. Drug: BYL719 BYL719 will be administered orally once daily on each day of the 28-day cycle.

Outcome Measures

Primary Outcome Measures

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

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
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center & Research Institute Moffitt 4	Tampa	Florida	United States	33612
2	University of Michigan Comprehensive Cancer Center SC	Ann Arbor	Michigan	United States	48109-0944
3	Karmanos Cancer Institute Dept of Onc	Detroit	Michigan	United States	48201
4	Washington University School of Medicine Onc Dept	Saint Louis	Missouri	United States	63110
5	Memorial Sloan Kettering Cancer Center Onc Dept	New York	New York	United States	10065
6	Vanderbilt University Medical Center Dept of Onc	Nashville	Tennessee	United States	37232
7	Cancer Therapy & Research Center / UT Health Science Center SC	San Antonio	Texas	United States	78229
8	Novartis Investigative Site	Parkville	Victoria	Australia	3050
9	Novartis Investigative Site	Bruxelles		Belgium	1200
10	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 2M9
11	Novartis Investigative Site	Lyon Cedex		France	69373
12	Novartis Investigative Site	Saint Herblain cedex		France	44805
13	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50937
14	Novartis Investigative Site	Milano	MI	Italy	20141
15	Novartis Investigative Site	Modena	MO	Italy	41100
16	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
17	Novartis Investigative Site	Amsterdam		Netherlands	1066 CX
18	Novartis Investigative Site	Singapore		Singapore	169610
19	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
20	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
21	Novartis Investigative Site	Madrid		Spain	28050
22	Novartis Investigative Site	Bellinzona		Switzerland	6500