check_circleStudy Completed

Neoplasms

Bayer Identifier:

16958

ClinicalTrials.gov Identifier:

NCT02592785

EudraCT Number:

Not Available

EU CT Number:

Not Available
Phase I dose escalation study of BAY 1163877 (Rogaratinib) in Japanese subjects with refractory, locally advanced or metastatic solid tumors

Trial purpose

Primary objectives of this study are to assess the safety and tolerability of BAY 1163877 in Japanese subjects with refractory, locally advanced or metastatic solid tumors and to characterize the PK of BAY 1163877

Key Participants Requirements

Sex

Both

Age

20 - N/A
  • - Japanese males or female aged ≥ 20 years
    - Histologically or cytologically confirmed refractory, locally advanced or metastatic solid tumors who are not candidates for standard therapy at discretion of investigator
    - High FGFR expression levels based on archival or fresh tumor biopsy specimen analysis. Bladder cancer subjects with low overall FGFR expression levels can be included if activating FGFR3 mutations are confirmed.
    - Subjects must have at least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
    - Life expectancy of at least 3 months
    - Recovery to National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v4.03) Grade < 2 level or recovery to baseline preceding the prior treatment from any previous drug / procedure-related toxicity (subjects with persistent alopecia, anemia, and/or hypothyroidism can be included)
    - Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2
    - Adequate bone marrow, liver and renal function
    - Prothrombin time-International normalized ratio (PT-INR) and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN. Subjects being treated with anticoagulant, e.g. warfarin or heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists


  • - History or current condition of an uncontrolled cardiovascular disease including congestive heart failure New York Heart Association (NYHA) > Class 2, unstable angina (symptoms of angina at rest) or new-onset angina (within last 3 months) or myocardial infarction within past 6 months and cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted)
    - Left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiography performed
    - Subjects with history and/or current evidence of endocrine alteration of calcium phosphate homeostasis (e.g. parathyroid disorder, history of parathyroidectomy, tumor lysis, tumoral calcinosis). Calcium (Ca) x (time) phosphate (PO4) should be < 70 mg²/dL².
    - Current evidence of corneal disorder / keratopathy including but not limited to bullous / band keratopathy, corneal abrasion, inflammation / ulceration, keratoconjunctivitis etc. (to be confirmed by ophthalmologic examination). Pre-existing cataract is not an exclusion criterion.
    - Moderate or severe hepatic impairment (subjects with Child-Pugh score B or C cannot be included.)
    - Known human immunodeficiency virus (HIV) infection
    - Subjects with an active hepatitis B and/or C infection requiring treatment
    - Anticancer chemotherapy or immunotherapy during the study or within 5-half-lives of anticancer chemotherapy or immunotherapy before start of study treatment.
    - Systolic blood pressure ≤ 110 and pulse rate ≥ 100/min, or diastolic blood pressure ≤ 70 mmHg and pulse rate ≥ 100/min
    - Uncontrolled hypertension as indicated by a resting systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg at screening

Trial summary

Enrollment Goal
9
Trial Dates
December 2015 - December 2017
Phase
Phase 1
Could I Receive a placebo
No
Products
Rogaratinib (BAY1163877)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Kashiwa, 277-8577, Japan
Completed
Koto-ku, 135-8550, Japan

Primary Outcome

  • Number of an Treatment Emergent Adverse Event
    date_rangeTime Frame:
    Up to 35 days after the last study drug administration
    enhanced_encryption
    Safety Issue:
    Yes
  • Intensity of an Treatment Emergent Adverse Event graded using the NCI-CTCAE version 4.03
    date_rangeTime Frame:
    Up tp 35 days after the last study drug administration
    enhanced_encryption
    Safety Issue:
    Yes
  • Maximum observed plasma concentration after single dose administration (Cmax) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Cmax divided by dose (mg) per kg body weight (Cmax,norm) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Cmax divided by dose (mg) (Cmax/D) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Area under the plasma concentration vs time curve from zero to 12 hours p.a. after first-dose administration (AUC(0-12)) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-12) divided by dose (mg) per kg body weight (AUC(0-12) norm) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-12) divided by dose (mg) (AUC(0-12)/D) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC from time zero to the last data point > LLOQ (lower limit of quantification) of BAY1163877 (AUC(0-tlast))
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tlast) divided by dose (mg) per kg body weight (AUC(0-tlast) norm) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tlast) divided by dose (mg) (AUC(0-tlast)/D) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUCnorm of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC/D of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Maximum Observed Drug Concentration in Plasma after multiple administrations (Cmax, md) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Cmax after multiple administrations divided by dose (mg) per kg body weight (Cmax,norm, md) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • Cmax after multiple administrations divided by dose (mg) (Cmax/Dmd) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-12) after multiple administrations (AUC(0-12)md) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-12) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-12)norm,md) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-12) divided by dose (mg) after multiple administrations (AUC(0-12)/Dmd) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tlast)after multiple administrations (AUC(0-tlast)md) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tlast) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-tlast) norm,md) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No
  • AUC(0-tlast) after multiple administrations divided by dose (mg) (AUC(0-tlast)/Dmd) of BAY1163877
    date_rangeTime Frame:
    On cycle 1, Day 15 during multiple-dose: before morning dose and 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose
    enhanced_encryption
    Safety Issue:
    No

Secondary Outcome

  • Tumor response evaluation based on RECIST 1.1
    date_rangeTime Frame:
    Screening, end of every second cycle (i.e., Cycle 2, 4, 6, 8,…)
    enhanced_encryption
    Safety Issue:
    No
  • FGF23 levels
    FGF 23: fibroblast growth factor 23
    date_rangeTime Frame:
    Cycle 1 (Days 1 and 15)
    enhanced_encryption
    Safety Issue:
    No
  • Phosphate levels
    date_rangeTime Frame:
    Cycle 1 (Days 1, 8, 15), Cycle 2 to 12 (Days 1, 8, 15), Cycle ≥13 (Days 1, 11), end of treatment
    enhanced_encryption
    Safety Issue:
    No
  • FGFR1/2/3 mRNA expression in tumor tissue to evaluate of biomarker status
    date_rangeTime Frame:
    At Screening visit
    enhanced_encryption
    Safety Issue:
    No

Trial design

An open label, Phase I study to evaluate the safety, tolerability, pharmacokinetics and efficacy of BAY 1163877 in Japanese subjects with refractory, locally advanced or metastatic solid tumors
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
N/A
Blinding
Open Label
Assignment
Single Group Assignment
Trial Arms
1

Additional Information

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