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.
Brief Title
A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies
Categories
Completion Date
Completion Date Type
Actual
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
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
* 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
Inclusion 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
inclusion/
* 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
inclusion/
Gender
All
Gender Based
false
Keywords
advanced solid tumors
lung cancer
bladder cancer
BGJ398
FGFR
kinase inhibitor
advanced solid malignancies
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01004224
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CBGJ398X2101
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome 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
Outcome 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)
Outcome Time Frame
23 months
Secondary Ids
Secondary Id
2009-010876-73
Secondary Outcomes
Outcome 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
Outcome Time Frame
23 months
Outcome 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)
Outcome Description
Time vs. concentration profiles, PK parameters of BGJ398 and known active metabolite(s).
Outcome Time Frame
23 months
Outcome Measure
To determine the pharmacokinetic (PK) profiles of oral BGJ398
Outcome Description
Pre- vs. post treatment serial changes in FGF23 plasma levels (not done for patients enrolled to expansion Arm 4)
Outcome Time Frame
23 months
Outcome Measure
To evaluate the pharmacodynamic effect of the drug.
Outcome Description
Overall tumor response rate (ORR) and PFS assessed by investigator per RECIST
Outcome Time Frame
23 months
Outcome Measure
Assess preliminary anti-tumor activity for patients not in Arm 4.
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404