Clinical trial NCT02592785: Phase I Dose Escalation Study of BAY 1163877 (Rogaratinib) in Japanese Subjects With Refractory, Locally Advanced or Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 9
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of an Treatment Emergent Adverse Event
timeFrame: Up to 35 days after the last study drug administration
measure: Intensity of an Treatment Emergent Adverse Event graded using the NCI-CTCAE version 4.03
timeFrame: Up tp 35 days after the last study drug administration
measure: Maximum observed plasma concentration after single dose administration (Cmax) of BAY1163877
timeFrame: 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
measure: Cmax divided by dose (mg) per kg body weight (Cmax,norm) of BAY1163877
timeFrame: 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
measure: Cmax divided by dose (mg) (Cmax/D) of BAY1163877
timeFrame: 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
measure: Area under the plasma concentration vs time curve from zero to 12 hours p.a. after first-dose administration (AUC(0-12)) of BAY1163877
timeFrame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
measure: AUC(0-12) divided by dose (mg) per kg body weight (AUC(0-12) norm) of BAY1163877
timeFrame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
measure: AUC(0-12) divided by dose (mg) (AUC(0-12)/D) of BAY1163877
timeFrame: On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
measure: AUC from time zero to the last data point > LLOQ (lower limit of quantification) of BAY1163877 (AUC(0-tlast))
timeFrame: 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
measure: AUC(0-tlast) divided by dose (mg) per kg body weight (AUC(0-tlast) norm) of BAY1163877
timeFrame: 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
measure: AUC(0-tlast) divided by dose (mg) (AUC(0-tlast)/D) of BAY1163877
timeFrame: 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
measure: AUC of BAY1163877
timeFrame: 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
measure: AUCnorm of BAY1163877
timeFrame: 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
measure: AUC/D of BAY1163877
timeFrame: 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
measure: Maximum Observed Drug Concentration in Plasma after multiple administrations (Cmax, md) of BAY1163877
timeFrame: 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
measure: Cmax after multiple administrations divided by dose (mg) per kg body weight (Cmax,norm, md) of BAY1163877
timeFrame: 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
measure: Cmax after multiple administrations divided by dose (mg) (Cmax/Dmd) of BAY1163877
timeFrame: 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
measure: AUC(0-12) after multiple administrations (AUC(0-12)md) of BAY1163877
timeFrame: 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
measure: AUC(0-12) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-12)norm,md) of BAY1163877
timeFrame: 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
measure: AUC(0-12) divided by dose (mg) after multiple administrations (AUC(0-12)/Dmd) of BAY1163877
timeFrame: 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
measure: AUC(0-tlast)after multiple administrations (AUC(0-tlast)md) of BAY1163877
timeFrame: 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
measure: AUC(0-tlast) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-tlast) norm,md) of BAY1163877
timeFrame: 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
measure: AUC(0-tlast) after multiple administrations divided by dose (mg) (AUC(0-tlast)/Dmd) of BAY1163877
timeFrame: 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
Secondary outcomes:
measure: Tumor response evaluation based on RECIST 1.1
timeFrame: Screening, end of every second cycle (i.e., Cycle 2, 4, 6, 8,…)
measure: FGF23 levels
timeFrame: Cycle 1 (Days 1 and 15)
measure: Phosphate levels
timeFrame: Cycle 1 (Days 1, 8, 15), Cycle 2 to 12 (Days 1, 8, 15), Cycle ≥13 (Days 1, 11), end of treatment
measure: FGFR1/2/3 mRNA expression in tumor tissue to evaluate of biomarker status
timeFrame: At Screening visit
Other outcomes:
Locations:
city: Kashiwa
country: Japan
state: Chiba
city: Koto-ku
country: Japan
state: Tokyo
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: