Open Label Regorafenib Study to Evaluate Cardiovascular Safety Parameters, Tolerability, and Anti-tumor Activity

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01339104
• Other study ID #: 14814
• Status: Completed
• Phase: Phase 1
• First received: April 19, 2011
• Last updated: September 30, 2014
• Start date: April 2011
• Est. completion date: August 2013

Study information

• Verified date: September 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Regorafenib (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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Effect on Left Ventricular Ejection Fraction (LVEF)		12 weeks post Cycle 1	Yes
Secondary	Decrease in tumor size based on investigator assessed RECIST criteria		3 years	Yes

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