A Dose Escalation Study in Adult Patients With Advanced Solid Malignancies

Phase 1

Completed

• 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
• Interventions: Drug: BGJ398

• Registration Number: NCT01004224
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-10-27
• Study First Submitted QC: 2009-10-28
• Study First Posted: 2009-10-29
• Study Start: 2009-12-11
• Primary Completion: 2018-10-08
• Study Completion: 2018-10-08
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-02
• Last Update Posted: 2019-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 208

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BGJ398	BGJ398	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
To determine the pharmacokinetic (PK) profiles of oral BGJ398	23 months	Time vs. concentration profiles, PK parameters of BGJ398 and known active metabolite(s).
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)

Trial Locations

Locations (4)

Thomas Jefferson University Hospital Onc Dept; 🇺🇸 Philadelphia, Pennsylvania, United States

Novartis Investigative Site; 🇹🇷 Izmir, Turkey

University of Colorado Dept. of Anschutz Cancer (3); 🇺🇸 Aurora, Colorado, United States

Memorial Sloan Kettering Cancer Center Onc. Dept..; 🇺🇸 New York, New York, United States