Advanced Solid Tumors With Alterations of FGFR1, 2 and or 3 Clinical Trial
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
| Verified date | October 2019 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The study will determine the maximum tolerated dose and thus the recommended phase II dose and schedule of the compound and characterize the safety.
| Status | Completed |
| Enrollment | 208 |
| Est. completion date | October 8, 2018 |
| Est. primary completion date | October 8, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Novartis Investigative Site | Heidelberg | Victoria |
| Austria | Novartis Investigative Site | Vienna | |
| France | Novartis Investigative Site | Bordeaux Cedex | |
| France | Novartis Investigative Site | Lyon Cedex | |
| France | Novartis Investigative Site | Marseille | |
| France | Novartis Investigative Site | Montpellier Cedex 5 | |
| France | Novartis Investigative Site | Paris | |
| France | Novartis Investigative Site | Saint-Herblain Cédex | |
| France | Novartis Investigative Site | Suresnes | |
| France | Novartis Investigative Site | Toulouse Cedex 9 | |
| France | Novartis Investigative Site | Villejuif Cedex | |
| Germany | Novartis Investigative Site | Essen | |
| Germany | Novartis Investigative Site | Hannover | |
| Germany | Novartis Investigative Site | Koeln | Nordrhein-Westfalen |
| Germany | Novartis Investigative Site | Marburg | |
| Israel | Novartis Investigative Site | Ramat Gan | |
| Israel | Novartis Investigative Site | Tel Aviv | |
| Italy | Novartis Investigative Site | Meldola | FC |
| Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
| Korea, Republic of | Novartis Investigative Site | Seoul | |
| Netherlands | Novartis Investigative Site | Amsterdam | |
| Netherlands | Novartis Investigative Site | Amsterdam | |
| Singapore | Novartis Investigative Site | Singapore | |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| Spain | Novartis Investigative Site | Barcelona | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Sevilla | Andalucia |
| Spain | Novartis Investigative Site | Valencia | Comunidad Valenciana |
| Taiwan | Novartis Investigative Site | Taipei | |
| Thailand | Novartis Investigative Site | Bangkok | |
| Thailand | Novartis Investigative Site | Chiang Mai | |
| Turkey | Novartis Investigative Site | Izmir | |
| United States | University of Colorado Dept. of Anschutz Cancer (3) | Aurora | Colorado |
| United States | Novartis Investigative Site | Boston | Massachusetts |
| United States | Novartis Investigative Site | Columbus | Ohio |
| United States | Novartis Investigative Site | Detroit | Michigan |
| United States | Novartis Investigative Site | Duarte | California |
| United States | Novartis Investigative Site | Los Angeles | California |
| United States | Novartis Investigative Site | Los Angeles | California |
| United States | Novartis Investigative Site | Memphis | Tennessee |
| United States | Novartis Investigative Site | Nashville | Tennessee |
| United States | Novartis Investigative Site | New Haven | Connecticut |
| United States | Memorial Sloan Kettering Cancer Center Onc. Dept.. | New York | New York |
| United States | Novartis Investigative Site | New York | New York |
| United States | Novartis Investigative Site | Philadelphia | Pennsylvania |
| United States | Thomas Jefferson University Hospital Onc Dept | Philadelphia | Pennsylvania |
| United States | Novartis Investigative Site | Pittsburgh | Pennsylvania |
| United States | Novartis Investigative Site | Salt Lake City | Utah |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Australia, Austria, France, Germany, Israel, Italy, Korea, Republic of, Netherlands, Singapore, Spain, Taiwan, Thailand, Turkey,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | 23 months | |
| Secondary | 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 | 23 months | |
| Secondary | To determine the pharmacokinetic (PK) profiles of oral BGJ398 | Time vs. concentration profiles, PK parameters of BGJ398 and known active metabolite(s). | 23 months | |
| Secondary | 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) | 23 months | |
| Secondary | Assess preliminary anti-tumor activity for patients not in Arm 4. | Overall tumor response rate (ORR) and PFS assessed by investigator per RECIST | 23 months |