check_circleStudy 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
  • - 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
  • - 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
24
Trial Dates
June 2013 - November 2015
Phase
Phase 1
Could I Receive a placebo
No
Products
Stivarga (Regorafenib, BAY73-4506)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-2: 0-24 hours
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 1-5: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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
    date_rangeTime Frame:
    Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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
    date_rangeTime Frame:
    Days 21-25: Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 24, 48 and 96 hours post-dose
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Up to 25 days
    enhanced_encryption
    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).
    date_rangeTime Frame:
    Up to 25 days
    enhanced_encryption
    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.
    date_rangeTime Frame:
    Up to 25 days
    enhanced_encryption
    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
    date_rangeTime Frame:
    Days 21-22: 0-24 hours
    enhanced_encryption
    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
    date_rangeTime Frame:
    Days 1-2: 0-10 hours
    enhanced_encryption
    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
    date_rangeTime Frame:
    Days 1-2: 10-24 hours
    enhanced_encryption
    Safety Issue:
    No
  • AE,ur(0-10) Stage 2 for metabolites M-7 and M-8
    based on non-compartmental PK evaluation
    date_rangeTime Frame:
    Days 21-22: 0-10 hours
    enhanced_encryption
    Safety Issue:
    No
  • AE,ur(10-24) Stage 2 for metabolites M-7 and M-8
    based on non-compartmental PK evaluation
    date_rangeTime Frame:
    Days 21-22: 10-24 hours
    enhanced_encryption
    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
2

Additional Information

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