Clinical trial NCT01004224: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-10-29
Enrollment: 208
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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)
timeFrame: 23 months
Secondary outcomes:
measure: 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)
timeFrame: 23 months
measure: To determine the pharmacokinetic (PK) profiles of oral BGJ398
timeFrame: 23 months
measure: To evaluate the pharmacodynamic effect of the drug.
timeFrame: 23 months
measure: Assess preliminary anti-tumor activity for patients not in Arm 4.
timeFrame: 23 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: Aurora
country: United States
facility: University of Colorado Dept. of Anschutz Cancer (3)
state: Colorado
city: New Haven
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Onc. Dept..
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital Onc Dept
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Memphis
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Montpellier Cedex 5
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Saint-Herblain Cédex
country: France
facility: Novartis Investigative Site
city: Suresnes
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Marburg
country: Germany
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: