Clinical trial NCT01339104: Open Label Regorafenib Study to Evaluate Cardiovascular Safety Parameters, Tolerability, and Anti-tumor Activity
Official title: An Open-label, Non-randomized Phase I Study of Regorafenib (BAY73-4506) to Evaluate Cardiovascular Safety Parameters, Tolerability, Pharmacokinetics, and Anti-tumor Activity in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Cardiovascular safety
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2011-04-20
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Open label Phase I study of Regorafenib to evaluate cardiovascular safety, tolerability and anti-tumor activity in patients with advanced solid tumors


Eligibility criteria: 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

Primary outcomes:
measure: Effect of regorafenib on cardiovascular safety parameters measured by change in QT\QTc on the ECG in patients with advanced solid tumors
timeFrame: After 8 weeks
measure: Effect on Left Ventricular Ejection Fraction (LVEF)
timeFrame: 12 weeks post Cycle 1
Secondary outcomes:
measure: Decrease in tumor size based on investigator assessed RECIST criteria
timeFrame: 3 years
Other outcomes:
Locations:
city: Aurora
country: United States
state: Colorado
city: Ann Arbor
country: United States
state: Michigan
city: St. Louis
country: United States
state: Missouri
city: Oklahoma City
country: United States
state: Oklahoma
city: Nashville
country: United States
state: Tennessee
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Jones RL, Bendell JC, Smith DC, Diefenbach K, Lettieri J, Boix O, Lockhart AC, O'Bryant C, Moore KN. A phase I open-label trial evaluating the cardiovascular safety of regorafenib in patients with advanced cancer. Cancer Chemother Pharmacol. 2015 Oct;76(4):777-84. doi: 10.1007/s00280-015-2827-3. Epub 2015 Aug 18.