Study Completed

Neoplasms

Bayer Identifier:

16653

ClinicalTrials.gov Identifier:

NCT01853046

EudraCT Number:

Not Available

EU CT Number:

Not Available

Pharmacokinetics and safety of regorafenib (BAY73-4506) in cancer subjects with severe renal impairment

Trial purpose

To characterize the pharmacokinetics and safety of regorafenib in cancer subjects with severe renal impairment when compared to the Control group (cancer subjects with normal or mildly impaired renal function)

Key Participants Requirements

Sex

Both

Age

18 - N/A

Inclusion Criteria
- Subjects with histologically confirmed, locally advanced or metastatic, refractory solid tumors who are not candidates for standard therapy
- Male or female subject ≥ 18 years of age
- Women of childbearing potential must have a negative urine pregnancy test performed within 7 days before start of study treatment
- Life expectancy at least 8 weeks
- Adequate bone marrow, and liver function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
- For subjects with NORMAL OR MILDLY IMPAIRED RENAL FUNCTION (Control group); to be tested within 7 days of starting the study treatment:
-- Estimated creatinine clearance (CLcr) ≥ 60 mL/min as calculated using the Cockcroft-Gault equation
- For subjects with SEVERELY IMPAIRED renal function; to be tested within 7 days of starting the study treatment:
-- CLcr 15-29 mL/min as calculated using the Cockcroft-Gault equation
Exclusion Criteria
- Symptomatic metastatic brain or meningeal tumors
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
- History of organ allograft
- Non-healing wound, skin ulcer, or bone fracture
- Pheochromocytoma
- Uncontrolled concurrent medical illness including uncontrolled hypertension
- History of cardiac disease
- Pleural effusion or ascites that causes respiratory compromise
- Interstitial lung disease with ongoing signs and symptoms at the time of screening
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medication
- Subjects with evidence or history of bleeding diathesis; any hemorrhage or bleeding event NCI-CTCAE Grade ≥ 3 or higher within 4 weeks of start of investigational treatment
- Dehydration NCI-CTCAEversion 4.0 Grade ≥ 1
- Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 attributed to any prior therapy/procedure (excluding alopecia or anemia or grade 2 neuropathy that is not reversible due to oxaliplatin)
- Seizure disorder requiring anticonvulsant therapy (such as steroids or anti-epileptics)
- For subjects with SEVERELY IMPAIRED renal function:
-- Renal failure requiring hemo- or peritoneal dialysis
-- Acute renal failure
-- Acute nephritis
-- Nephrotic syndrome

Trial summary

Enrollment Goal

Trial Dates

June 2013 - November 2015

Phase

Phase 1

Could I Receive a placebo

Products

Stivarga (Regorafenib, BAY73-4506)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed		Buffalo, 14263-0001, United States
Completed		Aurora, 80045, United States
Completed		Edmonton, T6G 1Z2, Canada
Completed		Montreal, H2L 4M1, Canada
Completed		Hamilton, L8V 5C2, Canada
Completed		Vancouver, V5Z 4E6, Canada
Completed		St. Louis, 63110, United States
Completed		Los Angeles, 90033, United States
Terminated		Lebanon, 03756, United States
Completed		Buffalo, 14263-0001, United States
Completed		Aurora, 80045, United States
Completed		Edmonton, T6G 1Z2, Canada
Completed		Montreal, H2L 4M1, Canada
Completed		Hamilton, L8V 5C2, Canada
Completed		Vancouver, V5Z 4E6, Canada
Completed		St. Louis, 63110, United States
Completed		Los Angeles, 90033, United States
Terminated		Lebanon, 03756, United States

Primary Outcome

AUC(0-tlast) [area under the concentration-time curve after single (first) dose from time zero to the last data point >LLOQ (lower limit of quantification)] for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation. The AUC(0-tlast) [Area Under the Concentration-time Curve After Single (First) Dose From Time Zero to the Last Data Point >LLOQ (Lower Limit of Quantification)] is a measure of systemic drug exposure from time 0 up to the time point at which the last measurable drug could be detectable, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
AE,ur(0-24) (amount of drug excreted via urine during the collection interval 0–24 hours post administration) for metabolites M-7 and M-8
Amount of drug excreted into urine during the collection interval 0-24 hours post dose was expressed as percentage of administered dose.
Time Frame:
Days 1-2: 0-24 hours
Safety Issue:
No

Secondary Outcome

AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation. AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
AUC(0-24) (AUC from time zero to 24 hours p.a. after single (first) dose administration) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation. The AUC is a measure of systemic drug exposure, which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample; AUC(0-24) is defined as AUC divided from zero to 24 hours after single (first) dose.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
Cmax (maximum drug concentration in plasma after Single (first) dose administration) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation.Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
tmax (time to reach maximum drug concentration in plasma after single (first) dose) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation.Tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). It is obtained by collecting a series of blood samples at various times after dosing, and measuring them for drug content.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
tlast (time of last data point >LLOQ) after single (first) dose for regorafenib and its pharmacologically active metabolites M-2 and M-5
based on non-compartmental PK evaluation.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
t1/2 (half-life associated with the terminal slope) after single (fisrt) dose for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation. t1/2 refers to the elimination of the drug. It is the time taken for the blood plasma concentration to reach half the concentration in the terminal phase of elimination. It is expressed in hours (h) and derived from the terminal slope of the concentration versus time curve.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
CL/F (total body clearance of drug after extravascular administration) after single (first) dose for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation.Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
Vz/F (apparent volume of distribution during terminal phase after single (first) oral administration) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation.Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time Frame:
Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
AUC(0-24)md ((AUC(0-24) after multiple-dose administration) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation.
Time Frame:
Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
Cmax,md (Cmax after multiple-dose administration) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation.Cmax refers to the highest measured drug concentration which is obtained by collecting a series of blood samples and measuring the concentrations of drug in each sample.
Time Frame:
Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
AUC(0-tlast)md (AUC(0-tlast) after multiple-dose administration) for regorafenib and its pharmacologically active metabolites M-2 and M-5
based on non-compartmental PK evaluation.
Time Frame:
Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
tmax,md (time to reach maximum drug concentration in plasma after multiple-dose administration) for regorafenib and its pharmacologically active metabolites M-2 and M-5
based on non-compartmental PK evaluation
Time Frame:
Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
tlast,md (tlast after multiple-dose administration) for regorafenib and its pharmacologically active metabolites M-2 and M-5
based on non-compartmental PK evaluation
Time Frame:
Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
Safety Issue:
No
RACmax (Accumulation ratio calculated from Cmax,md and Cmax) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation. Accumulation ratio based on maximum plasma concentration (Cmax) was calculated as ratio of Cmax,md and Cmax.
Time Frame:
Up to 25 days
Safety Issue:
No
RAAUC (Accumulation ratio calculated from AUC(0-24)md and AUC(0-24)) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation. RAAUC calculated as ratio of AUC(0-24)md and AUC(0-24).
Time Frame:
Up to 25 days
Safety Issue:
No
RLin (Linearity factor calculated as ratio from AUC(0-24)md and AUC) for regorafenib and its pharmacologically active metabolites M-2 and M-5
Based on non-compartmental PK evaluation. RLin is the linearity factor of PK after multiple administrations of identical doses calculated as ratio of AUC(0-24)md and AUC.
Time Frame:
Up to 25 days
Safety Issue:
No
AE,ur(0-24)md (AE,ur(0-24) after multiple-dose administration) for metabolites M-7 and M-8
based on non-compartmental PK evaluation
Time Frame:
Days 21-22: 0-24 hours
Safety Issue:
No
AE,ur(0-10) Stage 1 (amount of drug excreted via urine during the collection interval 0–10 hours post administration) for metabolites M-7 and M-8
based on non-compartmental PK evaluation
Time Frame:
Days 1-2: 0-10 hours
Safety Issue:
No
AE,ur(10-24) Stage 1 ((amount of drug excreted via urine during the collection interval 10–24 hours post administration) for metabolites M-7 and M-8
based on non-compartmental PK evaluation
Time Frame:
Days 1-2: 10-24 hours
Safety Issue:
No
AE,ur(0-10) Stage 2 for metabolites M-7 and M-8
based on non-compartmental PK evaluation
Time Frame:
Days 21-22: 0-10 hours
Safety Issue:
No
AE,ur(10-24) Stage 2 for metabolites M-7 and M-8
based on non-compartmental PK evaluation
Time Frame:
Days 21-22: 10-24 hours
Safety Issue:
No

Trial design

A Phase I, multi-center, non-randomized, open label, parallel-group study evaluating the pharmacokinetics and safety of regorafenib (BAY73-4506) in cancer subjects with severe renal impairment compared to a control group

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

Non-randomized

Blinding

Open Label

Assignment

Parallel Assignment

Trial Arms

Additional Information

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