NeoplasmsPhase 1NCT01976741

Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor (Rogaratinib)

A Phase 1 study testing Rogaratinib (BAY1163877) oral solution, Rogaratinib (BAY1163877) oral tablet and Rogaratinib (BAY1163877) 800 mg BID in people with Neoplasms, run by Bayer at 29 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This was the first study where BAY1163877 was given to humans. Impact of the study was to evaluate if patients with advanced solid cancers show advanced clinical benefit under the treatment with the pan FGFR inhibitor. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms
What is being tested?: Rogaratinib (BAY1163877) oral solution, Rogaratinib (BAY1163877) oral tablet and Rogaratinib (BAY1163877) 800 mg BID
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 168 participants
Where: 29 sitesin 7 countries
Study dates: 30 Dec 2013to 9 Jan 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

For dose escalation: Participants with any type of solid tumor (all comer) were eligible for dose escalation and dose expansion at MTD in Part 1; Participants enrolled for dose expansion (MTD expansion cohort "all comer") were stratified according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR mutation using archival or fresh tumor biopsy material
For expansion cohorts: Participants were eligible for Part 2 only if they have histological or cytological confirmed squamous non-small cell lung cancer (sqNSCLC), lung adenocarcinoma, head and neck cancer or bladder cancer (BC). All participants in Part 2 were stratified according to high FGFR expression levels FGFR mutation using archival or fresh tumor biopsy specimen. BC participants with low overall FGFR expression levels could be included if activating FGFR3 (FGFR tyrosine kinases 3) mutations were confirmed
Participants must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1))
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study Treatment
Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m^2 according to the modified diet in renal disease (MDRD) abbreviated formula

Who cannot join

Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors or FGFR-specific antibodies)
Concomitant therapies that cannot be discontinued or switched to a different medication prior to study entry that are known to increase serum phosphate levels are not permitted within 4 weeks prior to start of study treatment)
Anticancer chemotherapy or immunotherapy during the study or within 5-halflives prior to start of study treatment. Mitomycin C, nitrosoureas or monoclonal antibodies with anticancer activity (e.g. bevacizumab or cetuximab etc.) should not be given within 6 weeks before starting to receive study treatment or within 6 weeks of pre-treatment biopsy for biomarker (p-ERK1/2) studies

Trial locations and contacts

29 sites in 7 countries.

Country

City, postcode or hospital

29 sites in 7 countries

Germany9 sites

Study site
Cologne, North Rhine-Westphalia, 50937
Study site
Dresden, Saxony, 01307
Study site
Essen, North Rhine-Westphalia, 45147
Study site
Hamburg, 20246
Study site
Heidelberg, Baden-Wurttemberg, 69120
Study site
Magdeburg, 39120
Study site
Tübingen, Baden-Wurttemberg, 72076
Study site
Weiden, Bavaria, 92637
Study site
Würzburg, Bavaria, 97080

Other trials in Germany

France5 sites

Study site
Besançon, 25030
Study site
Créteil, 94010
Study site
Dijon, 21079
Study site
Lille, 59020
Study site
Lyon, 69008

Other trials in France

Spain4 sites

Study site
Barcelona, 08035
Study site
Madrid, 28034
Study site
Madrid, 28041
Study site
Valencia, 46014

Other trials in Spain

United States3 sites

Study site
Chicago, Illinois, 60611-2908
Study site
Chicago, Illinois
Study site
Pittsburgh, Pennsylvania, 15232

Other trials in United States

South Korea3 sites

Study site
Seoul, 03080
Study site
Seoul, 03722
Study site
Seoul, 135-710

Other trials in South Korea

Switzerland3 sites

Study site
Chur, Kanton Graubünden, 7000
Study site
Geneva, 1205
Study site
Sankt Gallen, Canton of St. Gallen, 9007

Other trials in Switzerland

Singapore2 sites

Study site
Singapore, 119228
Study site
Singapore, 169610

Other trials in Singapore

About this study

Official title: An Open Label, Non-randomized, Phase I Dose Escalation Study to Characterize Safety, Tolerability, Pharmacokinetics and Maximum Tolerated Dose of BAY1163877 in Subjects With Refractory, Locally Advanced or Metastatic Solid Tumors

This was the first study where BAY1163877 was given to humans. Impact of the study was to evaluate if patients with advanced solid cancers show advanced clinical benefit under the treatment with the pan FGFR inhibitor. Patients (all comers) received the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1163877. The relative bioavailability of liquid service formulation and tablets was determined.
After the MTD was defined patients with solid tumors (all comers), lung cancer (lung adenocarcinoma \& squamous non-small cell lung cancer), head and neck cancer or bladder cancer was enrolled according to their FGFR expression profile (biomarker stratification).
The study also assessed the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1163877.
BAY1163877 was given twice daily as oral application. Treatment was stopped if the tumor continued to grow, if side effects, which the patient cannot tolerate, occurred or if the patient decided to exit treatment.

Conditions: Neoplasms
Being tested: Rogaratinib (BAY1163877) oral solution, Rogaratinib (BAY1163877) oral tablet, Rogaratinib (BAY1163877) 800 mg BID
Keywords: Phase I, Dose escalation, refractory, locally advanced or metastatic solid tumor, Bladder cancer, squamous non-small cell lung cancer, pan-FGFR inhibitor, lung adenocarcinoma, head and neck cancer
Medical subject headings: Neoplasms, Neoplasm Metastasis, Urinary Bladder Neoplasms, Adenocarcinoma of Lung, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Rogaratinib (BAY1163877) oral solutionDrug
Participants received Rogaratinib oral solution as a single dose on Cycle 1 Day 1 (C1D1) and twice daily (BID) from Cycle 1 Day 3 (C1D3) onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.
Rogaratinib (BAY1163877) oral tabletDrug
Participants received Rogaratinib oral tablet as a single dose on C1D1 and BID from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.
Rogaratinib (BAY1163877) 800 mg BIDDrug
Participants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.

Study groups in NCT01976741
Study group	Role	What they receive
Rogaratinib total dose escalation	Experimental	Participants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution. Receives: Drug: Rogaratinib (BAY1163877) oral solution; Drug: Rogaratinib (BAY1163877) oral tablet
Rogaratinib dose expansion (All Comers)	Experimental	Participants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles. Receives: Drug: Rogaratinib (BAY1163877) 800 mg BID
Rogaratinib dose expansion (BC)	Experimental	Participants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles. Receives: Drug: Rogaratinib (BAY1163877) 800 mg BID
Rogaratinib dose expansion (SCCHN)	Experimental	Participants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles. Receives: Drug: Rogaratinib (BAY1163877) 800 mg BID
Rogaratinib dose expansion (sqNSCLC)	Experimental	Participants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles. Receives: Drug: Rogaratinib (BAY1163877) 800 mg BID

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20%
The MTD was defined as maximum dose at which the incidence of Dose Limiting Toxicities (DLTs) during Cycle 1 is below 20%. DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug. BID=twice daily.
Measured: Up to 21 days
Number of DLTs During Cycle 1
DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug.
Measured: Up to 21 days
Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ [lower limit of quantification] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ [lower limit of quantification] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Cmax,md (Cmax after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Cmax/Dmd (Cmax divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
AUC(0-12)md (AUC(0-12) after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
AUC(0-12)/Dmd (AUC(0-12) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15
AUC(0-tlast)md (AUC(0-tlast) after multiple dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
AUC(0-tlast)/Dmd (AUC(0-tlast) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
%AE,ur(0-12) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 12 Hours Post Administration) of BAY1163877
%AE,ur(0-12) (amount of drug excreted via urine during the collection interval 0 - 12 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Measured: On Cycle1, Day 1
%AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 24 Hours Post Administration) of BAY1163877
%AE,ur(0-24) (amount of drug excreted via urine during the collection interval 0 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Measured: On Cycle1, Day 1
%AE,ur(12-24) (Amount of Drug Excreted Via Urine During the Collection Interval 12 - 24 Hours Post Administration) of BAY1163877
%AE,ur(12-24) (amount of drug excreted via urine during the collection interval 12 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
Measured: On Cycle1, Day 1

Secondary outcomes (15)

Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
Response as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1: complete response (CR: disappearance of all target lesions), partial response (PR: at least a 30% decrease in the sum of diameters of target lesions taking as the reference the baseline sum of diameters), stable disease (SD: steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference, the smallest sum of diameters while in the trial), progressive disease (PD: at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study).
Measured: Up to 2 years
Progression-free Survival (PFS)
PFS was defined as the time (days) from the date of the first dose of study drug to the date of the first observed disease progression (radiological or clinical) or death due to any cause, if death occurred before progression was documented. PFS for participants without tumor progression at the time of analysis was censored at their last date of tumor evaluation.
Measured: Up to 2 years
Time to Progression (TTP)
TTP was defined as the time from start of study treatment until first observed disease progression (radiological or clinical). Progression is defined using RECIST v1.0, as at least a 20% increase in the sum of diameters of the target lesions, taking as a references the smallest sum on study.
Measured: Up to 2 years
Duration of Response (DOR)
DOR (for partial and complete response (PR/CR)) was defined as the time (days) from the first documented objective response of PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). DOR was calculated for responders only, i.e. participants with complete or partial response. Therefore, the dose escalation group is not displayed.
Measured: Up to 2 years
Duration of Treatment (DOT)
Measured: Up to 2 years
Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1
Change in serum FGF23 levels from baseline to C2D1 was reported as ratio to baseline (%).
Measured: From baseline to C2D1
Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study
Measured: From baseline up to 2 years
Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study
Measured: From baseline up to 2 years
Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15
Measured: From baseline up to Cycle 1, Day 15
Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877
In order to evaluate the relative bioavailability of the tablet formulation, tablet Cmax/D, AUC(0-tlast)/D, and AUC/D on Cycle 1, Day -3 were compared to solution Cmax/D, AUC(0-tlast)/D, AUC/D on Cycle 1, Day 1 for all analytes. The logarithms of the PK parameters were analyzed using analysis of variance (ANOVA) including participant and formulation effects. Based on these analyses, point estimates (LS-means) and exploratory 90% confidence intervals for the ratios (tablet/solution) of Cmax/D, AUC(0- tlast)/D, and AUC/D were calculated by re-transformation of the logarithmic data using the intra-individual standard deviation of the ANOVA.
Measured: On Cycle 1, Day -3 and Cycle 1, Day 1
Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Tmax (time to reach maximum drug concentration in plasma) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Tlast (time of last plasma concentration above LLOQ) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Median and full range were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
T1/2 (half-life associated with the terminal slope) of BAY1163877 after single dose administration on Cycle 1, Day -3 and Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Measured: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Tmax,md (time to reach maximum drug concentration in plasma after multiple-dose administration) of BAY1163877. Median and full range were reported.
Measured: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Tlast,md (time of last plasma concentration above LLOQ after multiple-dose administration) of BAY1163877. Median and full range were reported.
Measured: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Dec 20139 Jan 2020

First posted6 Nov 2013 (estimated)
Study start30 Dec 2013
Primary completion11 Mar 2019
Study completion9 Jan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by BayerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 168 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01976741
Sponsor's protocol ID: 16443
Other IDs: 2013-002155-15
Status last verified: Apr 2021
First submitted: 30 Oct 2013
Last updated: 6 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Schuler M, Cho BC, Sayehli CM, Navarro A, Soo RA, Richly H, Cassier PA, Tai D, Penel N, Nogova L, Park SH, Schostak M, Gajate P, Cathomas R, Rajagopalan P, Grevel J, Bender S, Boix O, Nogai H, Ocker M, Ellinghaus P, Joerger M. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Oct;20(10):1454-1466. doi: 10.1016/S1470-2045(19)30412-7. Epub 2019 Aug 9.
PubMed 31405822
Grunewald S, Politz O, Bender S, Heroult M, Lustig K, Thuss U, Kneip C, Kopitz C, Zopf D, Collin MP, Boemer U, Ince S, Ellinghaus P, Mumberg D, Hess-Stumpp H, Ziegelbauer K. Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models. Int J Cancer. 2019 Sep 1;145(5):1346-1357. doi: 10.1002/ijc.32224. Epub 2019 Mar 13.
PubMed 30807645

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All Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 6 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label, Non-randomized, Phase I Dose Escalation Study to Characterize Safety, Tolerability, Pharmacokinetics and Maximum Tolerated Dose of BAY1163877 in Subjects With Refractory, Locally Advanced or Metastatic Solid Tumors
ClinicalTrials.gov ID: NCT01976741
Acronym / sponsor ID: 16443
Conditions: Neoplasms
Keywords: Phase I, Dose escalation, refractory, locally advanced or metastatic solid tumor, Bladder cancer, squamous non-small cell lung cancer, pan-FGFR inhibitor, lung adenocarcinoma, head and neck cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 168 participants (actual)
Lead sponsor: BayerIndustry (pharma, biotech, devices)
Study start: 30 Dec 2013 (actual)
Primary completion: 11 Mar 2019 (actual)
Study completion: 9 Jan 2020 (actual)
First posted: 6 Nov 2013 (estimated)
Results: Posted 28 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This was the first study where BAY1163877 was given to humans. Impact of the study was to evaluate if patients with advanced solid cancers show advanced clinical benefit under the treatment with the pan FGFR inhibitor. Patients (all comers) received the study drug treatment in a dose-escalation scheme (no placebo group) to determine the safety, tolerability and maximum tolerated dose (MTD) of BAY1163877. The relative bioavailability of liquid service formulation and tablets was determined.
After the MTD was defined patients with solid tumors (all comers), lung cancer (lung adenocarcinoma \& squamous non-small cell lung cancer), head and neck cancer or bladder cancer was enrolled according to their FGFR expression profile (biomarker stratification).
The study also assessed the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1163877.
BAY1163877 was given twice daily as oral application. Treatment was stopped if the tumor continued to grow, if side effects, which the patient cannot tolerate, occurred or if the patient decided to exit treatment.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Rogaratinib total dose escalation	Experimental	Drug: Rogaratinib (BAY1163877) oral solution, Drug: Rogaratinib (BAY1163877) oral tabletParticipants with any type of solid tumor received escalating doses of Rogaratinib oral solution or tablet. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The participants in the 100 mg and 200 mg dose-escalation cohorts received oral solution and the participants in all the subsequent dose-escalation cohorts received tablet. And as an exception, on C1D-3 in the 200 mg dose-escalation cohort, the participants received tablet instead of oral solution.
Rogaratinib dose expansion (All Comers)	Experimental	Drug: Rogaratinib (BAY1163877) 800 mg BIDParticipants with cancer types other than bladder cancer (BC), squamous cell carcinoma of the head and neck (SCCHN), and squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.
Rogaratinib dose expansion (BC)	Experimental	Drug: Rogaratinib (BAY1163877) 800 mg BIDParticipants with bladder cancer (BC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.
Rogaratinib dose expansion (SCCHN)	Experimental	Drug: Rogaratinib (BAY1163877) 800 mg BIDParticipants with squamous cell carcinoma of the head and neck (SCCHN) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.
Rogaratinib dose expansion (sqNSCLC)	Experimental	Drug: Rogaratinib (BAY1163877) 800 mg BIDParticipants with squamous non-small cell lung cancer (sqNSCLC) received 800 mg Rogaratinib oral tablet b.i.d. (1600 mg/day) in 21-days cycles.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

For dose escalation: Participants with any type of solid tumor (all comer) were eligible for dose escalation and dose expansion at MTD in Part 1; Participants enrolled for dose expansion (MTD expansion cohort "all comer") were stratified according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR mutation using archival or fresh tumor biopsy material
For expansion cohorts: Participants were eligible for Part 2 only if they have histological or cytological confirmed squamous non-small cell lung cancer (sqNSCLC), lung adenocarcinoma, head and neck cancer or bladder cancer (BC). All participants in Part 2 were stratified according to high FGFR expression levels FGFR mutation using archival or fresh tumor biopsy specimen. BC participants with low overall FGFR expression levels could be included if activating FGFR3 (FGFR tyrosine kinases 3) mutations were confirmed
Participants must have measurable disease (Response evaluation criteria in solid tumors (RECIST 1.1))
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
Bone marrow, liver and renal functions as assessed by adequate laboratory methods to be conducted within 7 days prior to starting study Treatment

Key exclusion criteria (3 listed)

Previous treatment with anti-FGFR directed therapies (e.g. receptor tyrosine kinase inhibitors or FGFR-specific antibodies)
Concomitant therapies that cannot be discontinued or switched to a different medication prior to study entry that are known to increase serum phosphate levels are not permitted within 4 weeks prior to start of study treatment)
Anticancer chemotherapy or immunotherapy during the study or within 5-halflives prior to start of study treatment. Mitomycin C, nitrosoureas or monoclonal antibodies with anticancer activity (e.g. bevacizumab or cetuximab etc.) should not be given within 6 weeks before starting to receive study treatment or within 6 weeks of pre-treatment biopsy for biomarker (p-ERK1/2) studies

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Rogaratinib (BAY1163877) oral solutionParticipants received Rogaratinib oral solution as a single dose on Cycle 1 Day 1 (C1D1) and twice daily (BID) from Cycle 1 Day 3 (C1D3) onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.	Drug	Rogaratinib total dose escalation
Rogaratinib (BAY1163877) oral tabletParticipants received Rogaratinib oral tablet as a single dose on C1D1 and BID from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.	Drug	Rogaratinib total dose escalation
Rogaratinib (BAY1163877) 800 mg BIDParticipants received Rogaratinib 800 mg oral tablet as a single dose on C1D1 and BID (in total 1600 mg) from C1D3 onward for the remaining 19 days of Cycle 1. For subsequent cycles, study drug was administered twice daily for 21 days each Cycle.	Drug	Rogaratinib dose expansion (All Comers), Rogaratinib dose expansion (BC), Rogaratinib dose expansion (SCCHN), Rogaratinib dose expansion (sqNSCLC)

Primary outcome

Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20%
Time frame: Up to 21 days
The MTD was defined as maximum dose at which the incidence of Dose Limiting Toxicities (DLTs) during Cycle 1 is below 20%. DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug. BID=twice daily.
Number of DLTs During Cycle 1
Time frame: Up to 21 days
DLT was defined as any of the pre-defined adverse events occurring during Cycle 1 of a dose level and regarded by the investigators and/or sponsor to be related to the investigational drug.
Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Maximum drug concentration in plasma (Cmax) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-12) (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Area under the plasma concentration vs time curve from time zero to 12 hours (AUC(0-12)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ [lower limit of quantification] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-tlast) (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ [Lower Limit of Quantification]) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ [lower limit of quantification] (AUC(0-tlast)) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC (Area Under the Plasma Concentration vs Time Curve From Zero to Infinity) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Area under the plasma concentration vs time curve from zero to infinity (AUC) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Cmax/D (Maximum Drug Concentration in Plasma Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Maximum drug concentration in plasma divided by dose (Cmax/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-12)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to 12 Hours Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Area under the plasma concentration vs time curve from time zero to 12 hours divided by dose (AUC(0-12)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-tlast)/D (Area Under the Plasma Concentration vs Time Curve From Time Zero to the Last Data Point > LLOQ Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
Area under the plasma concentration vs time curve from time zero to the last data point > LLOQ divided by dose (AUC(0-tlast)/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1)
AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day -3. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC/D (AUC Divided by Dose) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2)
AUC divided by dose (AUC/D) of BAY1163877 after single dose administration on Cycle 1, Day 1. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Cmax,md (Cmax After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Cmax,md (Cmax after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Cmax/Dmd (Cmax Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Cmax/Dmd (Cmax divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-12)md (AUC(0-12) After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12)md (AUC(0-12) after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-12)/Dmd (AUC(0-12) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-12)/Dmd (AUC(0-12) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-tlast)md (AUC(0-tlast) After Multiple Dose Administration) of BAY1163877 on Cycle 1, Day 15
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast)md (AUC(0-tlast) after multiple dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
AUC(0-tlast)/Dmd (AUC(0-tlast) Divided by Dose After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
AUC(0-tlast)/Dmd (AUC(0-tlast) divided by dose after multiple-dose administration) of BAY1163877. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
%AE,ur(0-12) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 12 Hours Post Administration) of BAY1163877
Time frame: On Cycle1, Day 1
%AE,ur(0-12) (amount of drug excreted via urine during the collection interval 0 - 12 hours post administration, also expressed as percent of dose administered) of BAY1163877.
%AE,ur(0-24) (Amount of Drug Excreted Via Urine During the Collection Interval 0 - 24 Hours Post Administration) of BAY1163877
Time frame: On Cycle1, Day 1
%AE,ur(0-24) (amount of drug excreted via urine during the collection interval 0 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.
%AE,ur(12-24) (Amount of Drug Excreted Via Urine During the Collection Interval 12 - 24 Hours Post Administration) of BAY1163877
Time frame: On Cycle1, Day 1
%AE,ur(12-24) (amount of drug excreted via urine during the collection interval 12 - 24 hours post administration, also expressed as percent of dose administered) of BAY1163877.

15 secondary outcomes

Response Rate as Defined by RECIST Version 1.1 Reported as Number of Participants With Different Response Type
Time frame: Up to 2 years
Progression-free Survival (PFS)
Time frame: Up to 2 years
Time to Progression (TTP)
Time frame: Up to 2 years
Duration of Response (DOR)
Time frame: Up to 2 years
Duration of Treatment (DOT)
Time frame: Up to 2 years
Evaluation of Biomarker Status -Change in Serum FGF23 (Fibroblast Growth Factor 23) Levels From Baseline to C2D1
Time frame: From baseline to C2D1
Evaluation of Pharmacodynamic Parameters (PD) - Change of Heart Rate (HR) From Baseline to End of Study
Time frame: From baseline up to 2 years
Evaluation of Pharmacodynamic Parameters (PD) - Change of Blood Pressure (BP) From Baseline to End of Study
Time frame: From baseline up to 2 years
Evaluation of Pharmacodynamic Parameters (PD) - Change of QT Intervals From Baseline up to Cycle 1, Day 15
Time frame: From baseline up to Cycle 1, Day 15
Evaluation of Relative Bioavailability of the Tablet Formulation in Comparison to the Solution Formulation of BAY1163877
Time frame: On Cycle 1, Day -3 and Cycle 1, Day 1
Tmax (Time to Reach Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Tlast (Time of Last Plasma Concentration Above LLOQ) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
T1/2 (Half-life Associated With the Terminal Slope) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3 and Cycle 1, Day 1
Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hour(s) post-dose
Tmax,md (Time to Reach Maximum Drug Concentration in Plasma After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
Tlast,md (Time of Last Plasma Concentration Above LLOQ After Multiple-dose Administration) of BAY1163877 on Cycle 1, Day 15
Time frame: pre-dose (before morning dose), and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose

Results and safety

Results posted to the registry on 28 Apr 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Rogaratinib 50 mg BID	4	3
Rogaratinib 100 mg BID	4	4
Rogaratinib 200 mg BID	4	1
Rogaratinib 400 mg BID	3	2
Rogaratinib 600 mg BID	4	4
Rogaratinib 800 mg BID	4	4
Rogaratinib Dose Expansion (All Comers)	23	19
Rogaratinib Dose Expansion (BC)	74	62
Rogaratinib Dose Expansion (SCCHN)	8	7
Rogaratinib Dose Expansion (sqNSCLC)	40	36

Primary outcome: Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20%

Time frame: Up to 21 days. Number. Unit: mg BID

Measure	Rogaratinib Total Dose Escalation n = 21
Value	800

Population analysed: MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or DLT.

Primary outcome: Number of DLTs During Cycle 1

Time frame: Up to 21 days. Number. Unit: DLTs

Measure	Rogaratinib Total Dose Escalation n = 21
Value	0

Population analysed: MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or DLT.

Primary outcome: Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3

Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1). Geometric mean (Geometric Coefficient of Variation). Unit: µg/L

Measure	Rogaratinib 100 mg BID n = 4	Rogaratinib Expansion Food Effect n = 10
Value	2760 (56.5)	11300 (33.8)

Population analysed: All participants with valid pharmacokinetic (PK) data on Cycle 1, Day -3. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect.

Primary outcome: Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day 1

Time frame: pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day 1) and 48 hour(s) post-dose (Day 2). Geometric mean (Geometric Coefficient of Variation). Unit: µg/L

Measure	Rogaratinib 50 mg BID n = 3	Rogaratinib 100 mg BID n = 4	Rogaratinib 200 mg BID n = 4	Rogaratinib 400 mg BID n = 3	Rogaratinib 600 mg BID n = 4	Rogaratinib 800 mg BID n = 4	Rogaratinib 800 mg BID Pooled n = 51	Rogaratinib Expansion Food Effect n = 11	Rogaratinib Dose Expansion (All Comers) n = 19	Rogaratinib Dose Expansion (BC) n = 13	Rogaratinib Dose Expansion (SCCHN) n = 2	Rogaratinib Dose Expansion (sqNSCLC) n = 13
Value	3640 (16.8)	4360 (36.4)	5630 (46.2)	9480 (16.1)	9060 (32.3)	10200 (17.3)	11000 (34.3)	11000 (47.6)	10900 (32.5)	11000 (48.1)	13900 (52.6)	11200 (26.0)

Population analysed: All participants with valid PK data on Cycle 1, Day 1. Some of the participants from the expansion cohorts were included in Rogaratinib expansion food effect, and participants who received 800 mg BID in either escalation or expansion phase were combined as pre-specified in the Statistical Analysis Plan.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first study drug administration up to 30 days after the end of treatment with study drug.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rogaratinib Total Dose Escalation	9 of 23 (39.1%)	22 of 23 (95.7%)	3 of 23
Rogaratinib Dose Expansion (All Comers)	14 of 23 (60.9%)	23 of 23 (100%)	6 of 23
Rogaratinib Dose Expansion (BC)	44 of 74 (59.5%)	73 of 74 (98.6%)	17 of 74
Rogaratinib Dose Expansion (SCCHN)	5 of 8 (62.5%)	8 of 8 (100%)	2 of 8
Rogaratinib Dose Expansion (sqNSCLC)	24 of 40 (60%)	40 of 40 (100%)	12 of 40

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 31405822Schuler M, Cho BC, Sayehli CM, Navarro A, Soo RA, Richly H, Cassier PA, Tai D, Penel N, Nogova L, Park SH, Schostak M, Gajate P, Cathomas R, Rajagopalan P, Grevel J, Bender S, Boix O, Nogai H, Ocker M, Ellinghaus P, Joerger M. Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Oct;20(10):1454-1466. doi: 10.1016/S1470-2045(19)30412-7. Epub 2019 Aug 9.
Results publication: PubMed 30807645Grunewald S, Politz O, Bender S, Heroult M, Lustig K, Thuss U, Kneip C, Kopitz C, Zopf D, Collin MP, Boemer U, Ince S, Ellinghaus P, Mumberg D, Hess-Stumpp H, Ziegelbauer K. Rogaratinib: A potent and selective pan-FGFR inhibitor with broad antitumor activity in FGFR-overexpressing preclinical cancer models. Int J Cancer. 2019 Sep 1;145(5):1346-1357. doi: 10.1002/ijc.32224. Epub 2019 Mar 13.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bayer Study Director study director

Bayer

29 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in Germany, France, Spain, United States, South Korea and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose (MTD), Defined as Maximum Dose at Which the Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 is Below 20% (time frame: Up to 21 days). The study lists 27 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01976741, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.