Phase I Dose Escalation Study of BAY 1163877 (Rogaratinib) in Japanese Subjects With Refractory, Locally Advanced or Metastatic Solid Tumors

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02592785
• Other study ID #: 16958
• Status: Completed
• Phase: Phase 1
• First received: October 29, 2015
• Last updated: April 17, 2018
• Start date: December 15, 2015
• Est. completion date: December 6, 2017

Study information

• Verified date: April 2018
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 6, 2017
• Est. primary completion date: February 5, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• BAY1163877
Cohort 1: Single dose 600 mg on day 1, no drug on day 2 and then twice daily administration of the same dose for the remaining 19 days of cycle 1. From cycle 2 onwards all subjects are continuously treated for 21 days per cycle with twice daily administration of the same dose. Cohort 2: Single dose 800 mg on day 1, no drug on day 2 and then twice daily administration of the same dose for the remaining 19 days of cycle 1. From cycle 2 onwards all subjects are continuously treated for 21 days per cycle with twice daily administration of the same dose.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of an Treatment Emergent Adverse Event		Up to 35 days after the last study drug administration
Primary	Intensity of an Treatment Emergent Adverse Event graded using the NCI-CTCAE version 4.03		Up tp 35 days after the last study drug administration
Primary	Maximum observed plasma concentration after single dose administration (Cmax) of BAY1163877		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
Primary	Cmax divided by dose (mg) per kg body weight (Cmax,norm) of BAY1163877		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
Primary	Cmax divided by dose (mg) (Cmax/D) of BAY1163877		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
Primary	Area under the plasma concentration vs time curve from zero to 12 hours p.a. after first-dose administration (AUC(0-12)) of BAY1163877		On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
Primary	AUC(0-12) divided by dose (mg) per kg body weight (AUC(0-12) norm) of BAY1163877		On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
Primary	AUC(0-12) divided by dose (mg) (AUC(0-12)/D) of BAY1163877		On cycle 1, Day 1 to 3 (single-dose): Pre- dose, 0.5, 1, 2, 3, 4, 6, 8, 12 hours post-dose
Primary	AUC from time zero to the last data point > LLOQ (lower limit of quantification) of BAY1163877 (AUC(0-tlast))		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
Primary	AUC(0-tlast) divided by dose (mg) per kg body weight (AUC(0-tlast) norm) of BAY1163877		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
Primary	AUC(0-tlast) divided by dose (mg) (AUC(0-tlast)/D) of BAY1163877		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
Primary	AUC of BAY1163877		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
Primary	AUCnorm of BAY1163877		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
Primary	AUC/D of BAY1163877		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
Primary	Maximum Observed Drug Concentration in Plasma after multiple administrations (Cmax, md) of BAY1163877		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
Primary	Cmax after multiple administrations divided by dose (mg) per kg body weight (Cmax,norm, md) of BAY1163877		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
Primary	Cmax after multiple administrations divided by dose (mg) (Cmax/Dmd) of BAY1163877		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
Primary	AUC(0-12) after multiple administrations (AUC(0-12)md) of BAY1163877		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
Primary	AUC(0-12) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-12)norm,md) of BAY1163877		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
Primary	AUC(0-12) divided by dose (mg) after multiple administrations (AUC(0-12)/Dmd) of BAY1163877		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
Primary	AUC(0-tlast)after multiple administrations (AUC(0-tlast)md) of BAY1163877		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
Primary	AUC(0-tlast) after multiple administrations divided by dose (mg) per kg body weight (AUC(0-tlast) norm,md) of BAY1163877		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
Primary	AUC(0-tlast) after multiple administrations divided by dose (mg) (AUC(0-tlast)/Dmd) of BAY1163877		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	Tumor response evaluation based on RECIST 1.1		Screening, end of every second cycle (i.e., Cycle 2, 4, 6, 8,…)
Secondary	FGF23 levels	FGF 23: fibroblast growth factor 23	Cycle 1 (Days 1 and 15)
Secondary	Phosphate levels		Cycle 1 (Days 1, 8, 15), Cycle 2 to 12 (Days 1, 8, 15), Cycle =13 (Days 1, 11), end of treatment
Secondary	FGFR1/2/3 mRNA expression in tumor tissue to evaluate of biomarker status		At Screening visit

External Links

•   Click here and search for drug information provided by the FDA.
•   Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.