- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01287598
BAY73-4506 Probe Substrate Study
July 8, 2019 updated by: Bayer
A Phase I, Non-randomized Open-label Study to Evaluate the Effect of BAY73-4506 (Regorafenib) on Probe Substrates of CYP 2C9 (Warfarin), 2C19 (Omeprazole) and 3A4 (Midazolam) in a Cocktail Approach (Group A) and on a Probe Substrate of CYP 2C8 (Rosiglitazone, Group B) in Patients With Advanced Solid Tumors
- To evaluate the effect of BAY73-4506 on the pharmacokinetics of probe substrates of CYP 2C9 (warfarin), 2C19 (omeprazole) and 3A4 (midazolam) administered in a cocktail approach and on the pharmacokinetics of a probe substrate of CYP 2C8 (rosiglitazone)
- To evaluate safety, anti-tumor activity, pharmacokinetics, and pharmacodynamics of BAY73-4506 in patients with advanced solid tumors
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
41
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Alberta
-
Edmonton, Alberta, Canada, T6G 1Z2
- Cross Cancer Institute
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V5Z 4E6
- British Columbia Cancer Agency-Vancouver Centre
-
-
Ontario
-
Hamilton, Ontario, Canada, L8V 5C2
- Juravinski Cancer Centre
-
-
Quebec
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Montreal, Quebec, Canada, H3T 1E2
- Sir Mortimer B. Davis Jewish General Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Female and male subjects must be ≥ 18 years at the first screening examination / visit
- ECOG Performance Status of ≤ 2
- Histological or cytological documentation of confirmed advanced solid tumors. Subjects should have measurable or non-measurable disease according to RECIST
- Life Expectancy of at least 3 months
Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements conducted within 14 days prior to the first study treatment:
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count (ANC) ≥1,500/mm3
- Platelet count ≥ 100,000/ mm3
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2 times ULN
- ALT and AST ≤ 2.5 x ULN (≤ 5.0 x ULN for subjects with cancer involving the liver)
- 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 ULN
- INR and PTT ≤ 1.5 ULN
- Subjects who are therapeutically treated with warfarin, heparin or other anticoagulants are not eligible for study participation in Group A. Subjects who are therapeutically treated with warfarin, heparin or other anticoagulants, will be allowed to participate in Group B of the study provided they meet all eligibility criteria. Close monitoring of at least weekly evaluations will be performed until INR or PTT are stable by the local standard of care.
- Recovery from previous drug/procedure-related toxicities to CTC Grade 0 or 1 levels (except for alopecia), or to baseline preceding the prior treatment. Preexisting chemotherapy induced sensory neuropathy of CTC Grade ≤2 is not an exclusion criteria.
- Negative serum pregnancy test must be obtained within 7 days prior to the start of treatment in women of childbearing potential. Negative results must be available prior to study treatment.
- Subjects enrolled in this study must use adequate barrier birth control measures prior to, during the course of the study, and 3 months after the last administration of regorafenib.
- An adequate contraception includes the use of condoms or a vasectomy, hormonal contraception with implants or combined PO contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy. In addition, adequate birth control measures for the subject's partner is required, such as a hormonal contraception with implants or combined PO contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy, use of condoms or a vasectomy.
Exclusion Criteria:
- History of cardiac disease: Congestive heart failure (New York Heart Association, NYHA, Class III or IV) or active coronary artery disease (unstable angina [angina symptoms at rest] or new-onset angina [began within the last 3 months] or myocardial infarction within the past 6 months). Treatment with Type 1A or 3 anti-arrhythmics, such as Quinidine, Procainamide, Amiodarone, or Sotalol are not permitted. β-Blockers and digoxin are permitted.
- Left ventricular ejection fraction (LVEF) < 50% or below the LLN for the institution (whichever is higher).
- Subjects with pheochromocytoma
- Dehydration NCI-CTCAE, version 4, Grade > 1
- Uncontrolled hypertension (failure of diastolic blood pressure to fall to or below 90 mmHg or systolic blood pressure to fall to or below 140 mmHg with or without the use of antihypertensive drugs). At screening, subjects with history of hypertension should be on a stable anti-hypertensive treatment for at least 7 days prior to the first dose of study drug.
- Patients with known allergy to any of the study drug(s) to be administered, including known severe allergies, non-allergic drug reactions, or multiple drug allergies to any of the study drug(s) to be administered. This is also includes hypersensitivity to any of the compounds or excipients that will be administered to the study subject, specifically regorafenib, and warfarin, omeprazole and midazolam for subjects in Group A, or rosiglitazone for subjects in Group B.
- Subjects with arterial or venous thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism within 6 months before the start of study medication.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm 1
Regorafenib (Stivarga, BAY73-4506) + warfarin + omeprazole + midazolam
|
BAY73-4506 administered once a daily (od) in a 21-day on / 7-day off schedule
CYP 2C9 (warfarin) at Cycle 1
CYP 2C19 (omeprazole) at Cycle 1
CYP 3A4 (midazolam) at Cycle 1
|
EXPERIMENTAL: Arm 2
Regorafenib (Stivarga, BAY73-4506) + rosiglitazone
|
BAY73-4506 administered once a daily (od) in a 21-day on / 7-day off schedule
CYP2C8 (rosiglitazone) at Cycle 1
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Pharmacokinetics of probe substrates (AUC, Cmax, etc.)
Time Frame: Approximately 6 weeks
|
Approximately 6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Adverse event collection
Time Frame: Up to 3 years or longer if indicated
|
Up to 3 years or longer if indicated
|
Tumor Response evaluation measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time Frame: Up to 3 years or longer if indicated
|
Up to 3 years or longer if indicated
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
August 2, 2011
Primary Completion (ACTUAL)
July 3, 2018
Study Completion (ACTUAL)
July 30, 2018
Study Registration Dates
First Submitted
January 31, 2011
First Submitted That Met QC Criteria
January 31, 2011
First Posted (ESTIMATE)
February 1, 2011
Study Record Updates
Last Update Posted (ACTUAL)
July 10, 2019
Last Update Submitted That Met QC Criteria
July 8, 2019
Last Verified
July 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Gastrointestinal Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Anticoagulants
- Anti-Ulcer Agents
- Proton Pump Inhibitors
- Midazolam
- Rosiglitazone
- Warfarin
- Omeprazole
Other Study ID Numbers
- 12434
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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