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

NCT01339104 | Completed Phase 1

• 1 other identifier: 14814
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Neoplasms

Keywords

Cardiovascular safety

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Decrease in tumor size based on investigator assessed RECIST criteria

  3 years

Study Arms (1)

Regorafenib

EXPERIMENTAL

Drug: Regorafenib (Stivarga, BAY73-4506)

Interventions

Regorafenib (Stivarga, BAY73-4506) DRUG

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.

Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (6)

Unknown Facility

Aurora, Colorado, 80010, United States

Location

Unknown Facility

Ann Arbor, Michigan, 48109, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73104, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

Unknown Facility

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 26281907 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

regorafenib

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2011
• First Posted: April 20, 2011
• Study Start: April 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: October 1, 2014

Record last verified: 2014-09

Locations

US (6)