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BAY73-4506 Probe Substrate Study

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01287598
First received: January 31, 2011
Last updated: November 11, 2016
Last verified: November 2016
  Purpose
  • 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

Condition Intervention Phase
Neoplasms
Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Warfarin
Drug: Omeprazole
Drug: Midazolam
Drug: Rosiglitazone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Pharmacokinetics of probe substrates (AUC, Cmax, etc.) [ Time Frame: Approximately 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor Response evaluation measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: Yes ]
  • Adverse event collection [ Time Frame: Up to 3 years or longer if indicated ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: August 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Regorafenib (Stivarga, BAY73-4506) + warfarin + omeprazole + midazolam
Drug: Regorafenib (Stivarga, BAY73-4506)
BAY73-4506 administered once a daily (od) in a 21-day on / 7-day off schedule
Drug: Warfarin
CYP 2C9 (warfarin) at Cycle 1
Drug: Omeprazole
CYP 2C19 (omeprazole) at Cycle 1
Drug: Midazolam
CYP 3A4 (midazolam) at Cycle 1
Experimental: Arm 2
Regorafenib (Stivarga, BAY73-4506) + rosiglitazone
Drug: Regorafenib (Stivarga, BAY73-4506)
BAY73-4506 administered once a daily (od) in a 21-day on / 7-day off schedule
Drug: Rosiglitazone
CYP2C8 (rosiglitazone) at Cycle 1

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01287598

Locations
Canada, Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Hamilton, Ontario, Canada, L8V 5C2
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01287598     History of Changes
Other Study ID Numbers: 12434 
Study First Received: January 31, 2011
Last Updated: November 11, 2016
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

Keywords provided by Bayer:
Phase I
Probe substrate
target therapy
small molecule
pharmacokinetics

Additional relevant MeSH terms:
Midazolam
Omeprazole
Warfarin
Rosiglitazone
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Anticoagulants
Hypoglycemic Agents

ClinicalTrials.gov processed this record on December 07, 2016