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


Condition: Neoplasms

Intervention:

  • Drug: Rogaratinib (BAY1163877)

Purpose: - This is the first study where BAY1163877 is given to humans. Impact of the study is to evaluate if patients with advanced solid cancers show advanced clinical benefit under the treatment with the pan FGFR inhibitor. Patients (all comers) will receive 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 will be determined. - After the MTD is defined patients with solid tumors (all comers), lung cancer (lung adenocarcinoma & squamous non-small cell lung cancer), head and neck cancer or bladder cancer will be enrolled according to their FGFR expression profile (biomarker stratification). - The study will also assess the pharmacokinetics, biomarker status, pharmacodynamic parameters and tumor response of BAY1163877. - BAY1163877 will be given twice daily as oral application. Treatment will be stopped if the tumor continues to grow, if side effects, which the patient cannot tolerate, occur or if the patient decides to exit treatment.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01976741

Sponsor: Bayer

Primary Outcome Measures:

  • Measure: Maximum tolerated dose (MTD), defined as maximum dose at which the incidence of Drug Limiting Toxicities (DLTs) during cycle 1 is below 20%
  • Time Frame: up to 21 days
  • Safety Issue:
  • Measure: Cmax(maximum drug concentration in plasma after first dose administration)
  • Time Frame: Cycle 1 day -3 and cycle 1,day 1
  • Safety Issue:
  • Measure: AUC(0-12) (AUC from time zero to 12 hours p.a. after first-dose administration
  • Time Frame: Cycle 1 day -3 and cycle 1,day 1
  • Safety Issue:
  • Measure: AUC(0-tlast) (AUC from time zero to the last data point > LLOQ)
  • Time Frame: Cycle 1 day -3 and cycle 1,day 1
  • Safety Issue:
  • Measure: AUC (area under the plasma concentration vs time curve from zero to infinity after single (first) dose)
  • Time Frame: Cycle 1 day -3 and cycle 1,day 1
  • Safety Issue:
  • Measure: Cmax/D (maximum drug concentration in plasma after single dose administration divided by dose)
  • Time Frame: Cycle 1 day -3 and cycle 1,day 1
  • Safety Issue:
  • Measure: AUC(0-12)/D(AUC from time zero to 12 hours after single dose administration divided by dose)
  • Time Frame: Cycle 1 day -3 and cycle 1,day 1
  • Safety Issue:
  • Measure: AUC(0-tlast)/D (AUC from time zero to the last data point >>LLOQ(lower limit of quantification) after single dose administration divided by dose
  • Time Frame: Cycle 1 day -3 and cycle 1,day 1
  • Safety Issue:
  • Measure: AUC/D (AUC divided by dose)
  • Time Frame: Cycle 1 day -3 and cycle 1,day 1
  • Safety Issue:
  • Measure: Cmax,md (Cmax after multiple-dose administration)
  • Time Frame: Cycle1, day 15
  • Safety Issue:
  • Measure: Cmax/Dmd (Maximum drug concentration in plasma after multiple dose administration divided by dose)
  • Time Frame: Cycle1, day 15
  • Safety Issue:
  • Measure: AUC(0-12)md (AUC(0-12) after multiple-dose administration)
  • Time Frame: Cycle1, day 15
  • Safety Issue:
  • Measure: AUC(0-12)/Dmd (AUC from time zero to 12 hours after multiple dose administration divided by dose
  • Time Frame: Cycle1, day 15
  • Safety Issue:
  • Measure: AUC(0-tlast)md (AUC from time zero to the last data point>LLOQ after multiple dose administration)
  • Time Frame: Cycle1, day 15
  • Safety Issue:
  • Measure: AUC(0-tlast)/Dmd (AUC from time zero to the last data point>LLOQ after multiple dose administration divided by dose)
  • Time Frame: Cycle1, day 15
  • Safety Issue:
  • Measure: AE,ur(0-12) amount of drug excreted via urine during the collection interval 0 - 12 hours post administration
  • Time Frame: Cycle1, day 1
  • Safety Issue:
  • Measure: AE,ur(0-24) amount of drug excreted via urine during the collection interval 0 - 24 hours post administration
  • Time Frame: Cycle1, day 1
  • Safety Issue:
  • Measure: AE,ur(12-24) amount of drug excreted via urine during the collection interval 12 - 24 hours post administration
  • Time Frame: Cycle1, day 1
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Tumor response evaluation based on RECIST 1.1
  • Time Frame: up to 2 years
  • Safety Issue:
  • Measure: Evaluation of biomarker status
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Evaluation of Pharmacodynamic Parameters (PD)
  • Time Frame: Up to 2 years
  • Safety Issue:
  • Measure: Evaluation of relative bioabailability of the tablet formulation in comparison to the solution formulation of BAY1163877
  • Time Frame: Up to 2 years
  • Safety Issue:

Estimated Enrollment: 224

Study Start Date: December 30, 2013

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • For dose escalation: Subjects with any type of solid tumor (all comer) will be eligible for dose escalation and dose expansion at MTD in Part 1; Subjects enrolled for dose expansion (MTD expansion cohort "all comer") will be stratified according to high fibroblast growth factor receptor (FGFR) expression levels / FGFR mutation using archival or fresh tumor biopsy material
  • For expansion cohorts: Subjects will be 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 subjects in Part 2 will be stratified according to high FGFR expression levels FGFR mutation using archival or fresh tumor biopsy specimen. BC subjects with low overall FGFR expression levels can be included if activating FGFR3(FGFR tyrosine kinases3) mutations are confirmed
  • Subjects 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 m2 according to the modified diet in renal disease (MDRD) abbreviated formula

Exclusion Criteria:

  • 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

Contact:

  • Bayer Clinical Trials Contact
  • (+) 1-888-8422937

Locations:

  • Chicago Illinois 60611-2908 United States
  • Chicago Illinois United States
  • Pittsburgh Pennsylvania 15232 United States
  • Besancon 25030 France
  • Creteil 94000 France
  • Dijon 21000 France
  • Lille Cedex 59020 France
  • Lyon Cedex 69008 France
  • Heidelberg Baden-Württemberg 69120 Germany
  • Tübingen Baden-Württemberg 72076 Germany
  • Weiden Bayern 92637 Germany
  • Würzburg Bayern 97080 Germany
  • Bochum Nordrhein-Westfalen 44791 Germany
  • Essen Nordrhein-Westfalen 45147 Germany
  • Köln Nordrhein-Westfalen 50937 Germany
  • Dresden Sachsen 01307 Germany
  • Lübeck Schleswig-Holstein 23538 Germany
  • Jena Thüringen 07740 Germany
  • Hamburg 20246 Germany
  • Magdeburg 39120 Germany
  • Seoul 03080 Korea, Republic of
  • Seoul 120-752 Korea, Republic of
  • Seoul 135-710 Korea, Republic of
  • Singapore 119228 Singapore
  • Singapore 169610 Singapore
  • Barcelona 08035 Spain
  • Madrid 28034 Spain
  • Madrid 28041 Spain
  • Valencia 46014 Spain
  • Chur Graubünden 7000 Switzerland
  • St. Gallen Sankt Gallen 9007 Switzerland
  • Genève 1205 Switzerland

View trial on ClinicalTrials.gov


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