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

Purpose

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

Condition	Intervention	Phase
Neoplasms	Drug: Regorafenib (Stivarga, BAY73-4506)	Phase 1

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Regorafenib

U.S. FDA Resources

Further study details as provided by Bayer:

Primary Outcome Measures:

Effect of regorafenib on cardiovascular safety parameters measured by change in QT\QTc on the ECG in patients with advanced solid tumors [ Time Frame: After 8 weeks ] [ Designated as safety issue: Yes ]
Effect on Left Ventricular Ejection Fraction (LVEF) [ Time Frame: 12 weeks post Cycle 1 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Decrease in tumor size based on investigator assessed RECIST criteria [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment:	53
Study Start Date:	April 2011
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Regorafenib	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.

Arms

Assigned Interventions

Experimental: Regorafenib

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01339104

Locations

United States, Colorado

Aurora, Colorado, United States, 80010
United States, Michigan

Ann Arbor, Michigan, United States, 48109
United States, Missouri

St. Louis, Missouri, United States, 63110
United States, Oklahoma

Oklahoma City, Oklahoma, United States, 73104
United States, Tennessee

Nashville, Tennessee, United States, 37203
United States, Washington

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Bayer

Investigators

Study Director:

Bayer Study Director

Bayer

More Information

Additional Information:

Click here and search for drug information provided by the FDA. This link exits the ClinicalTrials.gov site

Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Head of Clinical Sciences, Bayer Healthcare Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:	NCT01339104 History of Changes
Other Study ID Numbers:	14814
Study First Received:	April 19, 2011
Last Updated:	April 11, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Bayer:

Cardiovascular safety

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on May 23, 2013