Clinical Trials /

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

NCT01976741

Description:

- 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.

Related Conditions:
  • Bladder Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 16443
  • SECONDARY ID: 2013-002155-15
  • NCT ID: NCT01976741

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
BAY1163877BAY1163877

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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
BAY1163877Experimental
  • BAY1163877

Eligibility Criteria

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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

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:
Description:

Secondary Outcome Measures

Measure:Tumor response evaluation based on RECIST 1.1
Time Frame:up to 2 years
Safety Issue:
Description:
Measure:Evaluation of biomarker status
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Evaluation of Pharmacodynamic Parameters (PD)
Time Frame:Up to 2 years
Safety Issue:
Description:
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:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial 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

Last Updated

January 22, 2017