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Effect of Regorafenib on Digoxin and Rosuvastatin in Patients With Advanced Solid Malignant Tumors.

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02106845
First Posted: April 8, 2014
Last Update Posted: November 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Bayer
  Purpose
Evaluate the effect of regorafenib on the pharmacokinetics of digoxin (P-gp substrate : P-glycoprotein) and rosuvastatin (BCRP substrate: Breast cancer resistant protein) by comparing their Area under time curve (AUC(0-24)) and maximum drug concentration (Cmax) on Day -7 and Cycle 1 or Cycle 2 Day 15 of regorafenib in cancer patients

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Multi-center, Non-randomized, Open Label, Drug-drug-interaction Study to Determine the Effect of Multiple Doses of Regorafenib (BAY 73-4506) on the Pharmacokinetics of Probe Substrates of Transport Proteins P-gp (Digoxin; Group A) and BCRP (Rosuvastatin; Group B) in Patients With Advanced Solid Malignant Tumors

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)) for Digoxin [ Time Frame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15 ]
  • Maximum drug concentration (Cmax) in plasma for Digoxin [ Time Frame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15 ]
  • Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)) for rosuvastatin [ Time Frame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15 ]
  • Maximum drug concentration (Cmax) in plasma for rosuvastatin [ Time Frame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15 ]

Secondary Outcome Measures:
  • Tumor Response following RECIST criteria [ Time Frame: From first dose up to 3 months after end of treatment ]
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 30 days after last dose ]
  • Number of participants with drug related adverse events as a measure of safety and tolerability [ Time Frame: Up to 30 days after last dose ]

Enrollment: 42
Actual Study Start Date: April 22, 2014
Estimated Study Completion Date: June 30, 2018
Primary Completion Date: April 27, 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: P-gp probe substrate(digoxin)+regorafenib Drug: Digoxin
Single dose of digoxin 0.5 mg (2 tablets 0.25 mg) orally without and with regorafenib
Drug: Regorafenib (Stivarga, BAY73-4506)
Once daily orally 160 mg (4 tablets 40 mg)
Experimental: Group B: BCRP probe substrate (rosuvastatin) + regorafenib Drug: Rosuvastatin
Single dose of rosuvastatin 5mg (1 tablet 5 mg) without and with regorafenib 160 mg q.d. (4 tablets 40 mg)
Drug: Regorafenib (Stivarga, BAY73-4506)
Once daily orally 160 mg (4 tablets 40 mg)

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Inclusion Criteria:
  • The following criteria apply to ALL patients starting the study treatment:

    • Patients with histologically confirmed, locally advanced or metastatic solid tumors refractory to standard therapy or in whom regorafenib is considered a standard treatment.
    • Male or Female Caucasian patients >/= 18 years of age
    • Women of childbearing potential and men must agree to use adequate contraception before entering the program until at least 8 weeks after the last study drug administration.
    • Life expectancy of at leat 12 weeks
    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
    • Adequate bone marrow and liver function
    • Estimated creatinine clearance (CLcr) ≥ 30 mL/min as calculated using the Cockroft-Gault (C-G) equation.
    • Thyroid Stimulating Hormone(TSH) within normal ranges.
  • The following inclusion criteria apply to Group A (digoxin + regorafenib) patients ONLY:

    • Potassium, magnesium and calcium blood levels within normal range according to the local laboratory.
  • The following inclusion criteria apply to Group B (rosuvastatin + regorafenib) patients ONLY:

    • Signed genetic informed consent. Patients must be able to understand and willing to sign the written informed consent intended to screen for BCRP and OATP1B1 polymorphisms.
  • Exclusion Criteria:
  • For ALL patients
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
  • Non-healing wound, skin ulcer, or bone fracture.
  • Ongoing or active infection.
  • Other anticancer treatment.
  • Patients unable to swallow oral medications
  • For Group A (digoxin + regorafenib):

    • Family history of sudden cardiac death.
  • For Group B (rosuvastatin + regorafenib):

    • Patients with porphyria.
    • Patients with intestinal or urinary obstructions.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02106845


Locations
Germany
Freiburg, Baden-Württemberg, Germany, 79106
Frankfurt, Hessen, Germany, 60488
Herne, Nordrhein-Westfalen, Germany, 44625
Hungary
Budapest, Hungary, 1083
Budapest, Hungary, 1122
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02106845     History of Changes
Other Study ID Numbers: 16674
2013-003613-18 ( EudraCT Number )
First Submitted: April 4, 2014
First Posted: April 8, 2014
Last Update Posted: November 8, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Regorafenib
Probe substrates
Pharmacokinetics
Cancer
Safety
Advanced solid malignant tumors

Additional relevant MeSH terms:
Neoplasms
Rosuvastatin Calcium
Digoxin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Anti-Arrhythmia Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs