Phase 1b Trial of BGJ398/BYL719 in Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01928459
First received: August 21, 2013
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Advanced Solid Tumors,
Metastatic Solid Tumors
Drug: BGJ398
Drug: BYL719
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719 [ Time Frame: Approximately 8 months ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Every 28 days from baseline visit until end of study visit ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Every two months from the date of baseline CT scan ] [ Designated as safety issue: No ]
    Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719; Overall response rate = complete response + partial response

  • Progression free survival [ Time Frame: Every two months from the date of baseline CT scan ] [ Designated as safety issue: No ]
    Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719

  • Time vs. concentration profile of BGJ398 and BYL719 [ Time Frame: Every 28 days for up to 10 cycles ] [ Designated as safety issue: Yes ]
    Plasma concentration versus time profiles. Plasma PK parameters will be used to characterize the PK profiles of the combination of BGJ398 with BYL719


Estimated Enrollment: 55
Study Start Date: October 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01928459

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 27 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01928459     History of Changes
Other Study ID Numbers: CBGJ398X2102
Study First Received: August 21, 2013
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
BGJ398, BYL719, advanced solid tumor, metastatic breast cancer, PK3CA, FGFR, fibroblast growth factor receptor,

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 28, 2014