Neoplasms
Conditions
Keywords
Cardiovascular safety
Brief summary
Open label Phase I study of Regorafenib to evaluate cardiovascular safety, tolerability and anti-tumor activity in patients with advanced solid tumors
Interventions
DRUGRegorafenib (Stivarga, BAY73-4506)
All subjects will receive regorafenib administered from Day 1 -21 at a dose of 160 mg od (4 x 40 mg tablets) followed by a 7 days break in repeating cycles of 28 days. The drug is to be taken in the morning with approximately 240 mL of water after having a low fat breakfast. Holter ECGs with triplicate measurements will automatically be obtained at specified timepoints over 24 hours on days -1 and Cycle 1, Day 21. PK samples will be drawn on Cycle 1, Day 21. PK timepoints are time-matched with Holter ECG timepoints. 24 hour urine will be collected beginning on Cycle 1, Day 21. MUGA scans will be done at screening, Cycle 2 Day 21 (after 42 doses of BAY73-4506), then every 3 cycles starting in Cycle 5, and at end of treatment.
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects \>/= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 * Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to dosing: * Hemoglobin (Hb) \>/= 9.0 g/dL, Absolute neutrophil count (ANC) \>/= 1500/mm³, Platelet \>/= 100,000/mm³, Total bilirubin \</= 1.5 times upper limit of normal (ULN), Alkaline phosphatase \</= 4 x ULN * Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) \</= 2.5 times ULN (\</= 5.0 x ULN for subjects with liver involvement of their cancer), International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) \< 1.5 x ULN, Serum creatinine \</= 1.5 times ULN and glomerular filtration rate (GFR) \>/= 30 ml/min/1.73 m² according to the MDRD (Modified Diet in Renal Disease) abbreviated formula, Lipase \</= 1.5 x ULN * Left Ventricular Ejection Fraction (LVEF) \>/= 50 % as assessed at the Baseline Multigated Acquisition (MUGA) scan * QTc (Q-T corrected) \</= 470 msec at Screening * Having advanced, refractory disease * Life expectancy of at least 3 months * Recovery from any previous drug/procedure-related toxicity to Common Toxicological Criteria (CTC) Grade 0 or 1 levels (except alopecia), or to baseline preceding the prior treatment.
Exclusion criteria
* History of cardiac disease: congestive heart failure \> New York Heart Association (NYHA) Class II; active coronary artery disease (unstable angina \[anginal symptoms at rest\] or new-onset angina \[began within the last 3 months\] or myocardial infarction within the past 6 months). * Uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of \>/= 3 antihypertensive drugs or systolic blood pressure greater than 150 mmHg) * History of or known human immunodeficiency virus (HIV) infection or active hepatitis B or C. * Subjects with serious non-healing wound, ulcer, or bone fracture * Subjects with arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before start of study medication * Persistent proteinuria of CTC Grade 3 or higher (\> 3.5 g/24 hours, measured by urine protein/creatinine ratio on a random urine sample) * Symptomatic metastatic brain or meningeal tumors unless the subject is \> 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within 2 weeks prior to study entry, and is clinically stable with respect to the tumor at the time of study entry * Clinically significant bleeding (CTC AE Grade 3 or higher) within 30 days before start of study medication. * Subjects with seizure disorder requiring anticonvulsant medication * History of organ allograft
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Effect of regorafenib on cardiovascular safety parameters measured by change in QT\QTc on the ECG in patients with advanced solid tumors | After 8 weeks |
| Effect on Left Ventricular Ejection Fraction (LVEF) | 12 weeks post Cycle 1 |
Secondary
| Measure | Time frame |
|---|---|
| Decrease in tumor size based on investigator assessed RECIST criteria | 3 years |
Countries
United States
Outcome results
None listed