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A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01004224
Collaborator
(none)
208
Enrollment
50
Locations
1
Arm
105.9
Actual Duration (Months)
4.2
Patients Per Site
0
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
208 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 11, 2009
Actual Primary Completion Date :
Oct 8, 2018
Actual Study Completion Date :
Oct 8, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: BGJ398

Drug: BGJ398

Outcome Measures

Primary Outcome Measures

  1. 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) [23 months]

    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

  1. 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) [23 months]

    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

  2. To determine the pharmacokinetic (PK) profiles of oral BGJ398 [23 months]

    Time vs. concentration profiles, PK parameters of BGJ398 and known active metabolite(s).

  3. To evaluate the pharmacodynamic effect of the drug. [23 months]

    Pre- vs. post treatment serial changes in FGF23 plasma levels (not done for patients enrolled to expansion Arm 4)

  4. Assess preliminary anti-tumor activity for patients not in Arm 4. [23 months]

    Overall tumor response rate (ORR) and PFS assessed by investigator per RECIST

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Novartis Investigative Site Duarte California United States 91010 3000
2 Novartis Investigative Site Los Angeles California United States 90033
3 Novartis Investigative Site Los Angeles California United States 90095
4 University of Colorado Dept. of Anschutz Cancer (3) Aurora Colorado United States 80045
5 Novartis Investigative Site New Haven Connecticut United States 06520
6 Novartis Investigative Site Boston Massachusetts United States 02114
7 Novartis Investigative Site Detroit Michigan United States 48201
8 Memorial Sloan Kettering Cancer Center Onc. Dept.. New York New York United States 10021
9 Novartis Investigative Site New York New York United States 10029
10 Novartis Investigative Site Columbus Ohio United States 43221
11 Novartis Investigative Site Philadelphia Pennsylvania United States 19104
12 Thomas Jefferson University Hospital Onc Dept Philadelphia Pennsylvania United States 19107-5098
13 Novartis Investigative Site Pittsburgh Pennsylvania United States 15232
14 Novartis Investigative Site Memphis Tennessee United States 38120
15 Novartis Investigative Site Nashville Tennessee United States 37203
16 Novartis Investigative Site Salt Lake City Utah United States 84103
17 Novartis Investigative Site Heidelberg Victoria Australia 3084
18 Novartis Investigative Site Vienna Austria A-1100
19 Novartis Investigative Site Bordeaux Cedex France 33075
20 Novartis Investigative Site Lyon Cedex France 69373
21 Novartis Investigative Site Marseille France 13273
22 Novartis Investigative Site Montpellier Cedex 5 France 34298
23 Novartis Investigative Site Paris France 75015
24 Novartis Investigative Site Saint-Herblain Cédex France 44805
25 Novartis Investigative Site Suresnes France 92150
26 Novartis Investigative Site Toulouse Cedex 9 France 31059
27 Novartis Investigative Site Villejuif Cedex France 94805
28 Novartis Investigative Site Koeln Nordrhein-Westfalen Germany 50937
29 Novartis Investigative Site Essen Germany 45147
30 Novartis Investigative Site Hannover Germany 30625
31 Novartis Investigative Site Marburg Germany 35039
32 Novartis Investigative Site Ramat Gan Israel 5265601
33 Novartis Investigative Site Tel Aviv Israel 6423906
34 Novartis Investigative Site Meldola FC Italy 47014
35 Novartis Investigative Site Seoul Korea Korea, Republic of 05505
36 Novartis Investigative Site Seoul Korea, Republic of 03080
37 Novartis Investigative Site Amsterdam Netherlands 1066 CX
38 Novartis Investigative Site Amsterdam Netherlands 1081 HV
39 Novartis Investigative Site Singapore Singapore 169610
40 Novartis Investigative Site Sevilla Andalucia Spain 41013
41 Novartis Investigative Site Barcelona Catalunya Spain 08035
42 Novartis Investigative Site Valencia Comunidad Valenciana Spain 46009
43 Novartis Investigative Site Barcelona Spain 08041
44 Novartis Investigative Site Madrid Spain 28009
45 Novartis Investigative Site Madrid Spain 28041
46 Novartis Investigative Site Madrid Spain 28050
47 Novartis Investigative Site Taipei Taiwan 10048
48 Novartis Investigative Site Bangkok Thailand 10330
49 Novartis Investigative Site Chiang Mai Thailand 50200
50 Novartis Investigative Site Izmir Turkey 35040

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01004224
Other Study ID Numbers:
  • CBGJ398X2101
  • 2009-010876-73
First Posted:
Oct 29, 2009
Last Update Posted:
Oct 4, 2019
Last Verified:
Oct 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
advanced solid tumors
lung cancer
bladder cancer
BGJ398
FGFR
kinase inhibitor
advanced solid malignancies
Additional relevant MeSH terms:
Neoplasms
Urinary Bladder Neoplasms
Infigratinib

Study Results

No Results Posted as of Oct 4, 2019