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A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

Primary Purpose

Advanced Solid Tumors With Alterations of FGFR1, 2 and or 3, Squamous Lung Cancer With FGFR1 Amplification, Bladder Cancer With FGFR3 Mutation or Fusion

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BGJ398
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumors With Alterations of FGFR1, 2 and or 3 focused on measuring advanced solid tumors, lung cancer, bladder cancer, BGJ398, FGFR, kinase inhibitor, advanced solid malignancies

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with histologically/cytologically confirmed advanced solid tumors with FGFR1 or FGFR2 amplification or FGFR3 mutation, for which no further effective standard anticancer treatment exists
  • Adequate bone marrow function
  • Adequate hepatic and renal function
  • Adequate cardiovascular function

  • Contraception.

    • For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period; must have a negative serum or urine pregnancy test and must not be nursing.
    • For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after the treatment period

Exclusion Criteria:

  • Patients with primary CNS tumor or CNS tumor involvement
  • Patients with history and/or current evidence of endocrine alteration of calcium-phosphate homeostasis
  • History and/or current evidence of ectopic mineralization/ calcification including but not limited to the soft tissue, kidneys, intestine, myocard and lung with the exception of calcified lymphnodes and asymptomatic coronary calcification
  • Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis etc., confirmed by ophthalmologic examination.
  • History or current evidence of cardiac arrhythmia and/or conduction abnormality
  • Women who are pregnant or nursing.

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • University of Colorado Dept. of Anschutz Cancer (3)
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Memorial Sloan Kettering Cancer Center Onc. Dept..
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Thomas Jefferson University Hospital Onc Dept
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BGJ398

Arm Description

Outcomes

Primary Outcome Measures

Incidence rate and category of dose-limiting toxicities will be tabulated for patients included in the dose escalation portion of the study, to establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPTD)
Incidence rate and category of dose-limiting toxicities will be tabulated for patients included in the dose escalation portion of the study, to establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPTD). This will be calculated using an established statistical model, based on incidence of adverse events and serious adverse events, physical examinations, vital signs, electrocardiograms, and laboratory parameters

Secondary Outcome Measures

To assess preliminary anti-tumor activity of BGJ398 for patients in expansion Arm 4 (previously treated patients with advanced/metastatic UCC with FGFR3 gene alterations)
overall response rate (ORR), as assessed by investigator per RECIST v 1.0; overall survival (OS), duration of response (DOR) and disease control rate (DCR) will be assessed
To determine the pharmacokinetic (PK) profiles of oral BGJ398
Time vs. concentration profiles, PK parameters of BGJ398 and known active metabolite(s).
To evaluate the pharmacodynamic effect of the drug.
Pre- vs. post treatment serial changes in FGF23 plasma levels (not done for patients enrolled to expansion Arm 4)
Assess preliminary anti-tumor activity for patients not in Arm 4.
Overall tumor response rate (ORR) and PFS assessed by investigator per RECIST

Full Information

First Posted
October 27, 2009
Last Updated
October 2, 2019
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01004224
Brief Title
A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies
Official Title
A Phase I, Open-label, Multi-center, Dose Escalation Study of Oral BGJ398, a Pan FGF-R Kinase Inhibitor, in Adult Patients With Advanced Solid Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
December 11, 2009 (Actual)
Primary Completion Date
October 8, 2018 (Actual)
Study Completion Date
October 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The study will determine the maximum tolerated dose and thus the recommended phase II dose and schedule of the compound and characterize the safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumors With Alterations of FGFR1, 2 and or 3, Squamous Lung Cancer With FGFR1 Amplification, Bladder Cancer With FGFR3 Mutation or Fusion, Advanced Solid Tumors With FGFR1 Amplication, Advanced Solid Tumors With FGFR2 Amplication, Advanced Solid Tumors With FGFR3 Mutation
Keywords
advanced solid tumors, lung cancer, bladder cancer, BGJ398, FGFR, kinase inhibitor, advanced solid malignancies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
208 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BGJ398
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
BGJ398
Primary Outcome Measure Information:
Title
Incidence rate and category of dose-limiting toxicities will be tabulated for patients included in the dose escalation portion of the study, to establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPTD)
Description
Incidence rate and category of dose-limiting toxicities will be tabulated for patients included in the dose escalation portion of the study, to establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPTD). This will be calculated using an established statistical model, based on incidence of adverse events and serious adverse events, physical examinations, vital signs, electrocardiograms, and laboratory parameters
Time Frame
23 months
Secondary Outcome Measure Information:
Title
To assess preliminary anti-tumor activity of BGJ398 for patients in expansion Arm 4 (previously treated patients with advanced/metastatic UCC with FGFR3 gene alterations)
Description
overall response rate (ORR), as assessed by investigator per RECIST v 1.0; overall survival (OS), duration of response (DOR) and disease control rate (DCR) will be assessed
Time Frame
23 months
Title
To determine the pharmacokinetic (PK) profiles of oral BGJ398
Description
Time vs. concentration profiles, PK parameters of BGJ398 and known active metabolite(s).
Time Frame
23 months
Title
To evaluate the pharmacodynamic effect of the drug.
Description
Pre- vs. post treatment serial changes in FGF23 plasma levels (not done for patients enrolled to expansion Arm 4)
Time Frame
23 months
Title
Assess preliminary anti-tumor activity for patients not in Arm 4.
Description
Overall tumor response rate (ORR) and PFS assessed by investigator per RECIST
Time Frame
23 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histologically/cytologically confirmed advanced solid tumors with FGFR1 or FGFR2 amplification or FGFR3 mutation, for which no further effective standard anticancer treatment exists Adequate bone marrow function Adequate hepatic and renal function Adequate cardiovascular function Contraception. For women: Must be surgically sterile, post-menopausal, or compliant with a medically approved contraceptive regimen during and for 3 months after the treatment period; must have a negative serum or urine pregnancy test and must not be nursing. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 3 months after the treatment period Exclusion Criteria: Patients with primary CNS tumor or CNS tumor involvement Patients with history and/or current evidence of endocrine alteration of calcium-phosphate homeostasis History and/or current evidence of ectopic mineralization/ calcification including but not limited to the soft tissue, kidneys, intestine, myocard and lung with the exception of calcified lymphnodes and asymptomatic coronary calcification Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis etc., confirmed by ophthalmologic examination. History or current evidence of cardiac arrhythmia and/or conduction abnormality Women who are pregnant or nursing. Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Duarte
State/Province
California
ZIP/Postal Code
91010 3000
Country
United States
Facility Name
Novartis Investigative Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Novartis Investigative Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Colorado Dept. of Anschutz Cancer (3)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Novartis Investigative Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Novartis Investigative Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Onc. Dept..
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Novartis Investigative Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Novartis Investigative Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
Novartis Investigative Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson University Hospital Onc Dept
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107-5098
Country
United States
Facility Name
Novartis Investigative Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Novartis Investigative Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Novartis Investigative Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Novartis Investigative Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84103
Country
United States
Facility Name
Novartis Investigative Site
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Novartis Investigative Site
City
Vienna
ZIP/Postal Code
A-1100
Country
Austria
Facility Name
Novartis Investigative Site
City
Bordeaux Cedex
ZIP/Postal Code
33075
Country
France
Facility Name
Novartis Investigative Site
City
Lyon Cedex
ZIP/Postal Code
69373
Country
France
Facility Name
Novartis Investigative Site
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier Cedex 5
ZIP/Postal Code
34298
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Saint-Herblain Cédex
ZIP/Postal Code
44805
Country
France
Facility Name
Novartis Investigative Site
City
Suresnes
ZIP/Postal Code
92150
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Novartis Investigative Site
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Novartis Investigative Site
City
Koeln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
50937
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Marburg
ZIP/Postal Code
35039
Country
Germany
Facility Name
Novartis Investigative Site
City
Ramat Gan
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Novartis Investigative Site
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Novartis Investigative Site
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41013
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46009
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35040
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

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