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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Bayer
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT02106845
First received: April 4, 2014
Last updated: August 29, 2014
Last verified: August 2014
  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
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor Response following RECIST criteria [ Time Frame: From first dose up to 3 months after end of treatment ] [ Designated as safety issue: No ]
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 30 days after last dose ] [ Designated as safety issue: Yes ]
  • Number of participants with drug related adverse events as a measure of safety and tolerability [ Time Frame: Up to 30 days after last dose ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: April 2014
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: July 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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: NCT02106845

Contacts
Contact: Bayer Clinical Trials Contact clinical-trials-contact@bayerhealthcare.com
Contact: For trial location information (Phone Menu Options '3' or '4') (+)1-888-84 22937

Locations
Germany
Not yet recruiting
Freiburg, Baden-Württemberg, Germany, 79106
Recruiting
Frankfurt, Hessen, Germany, 60488
Not yet recruiting
Herne, Nordrhein-Westfalen, Germany, 44625
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02106845     History of Changes
Other Study ID Numbers: 16674, 2013-003613-18
Study First Received: April 4, 2014
Last Updated: August 29, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy

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

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

ClinicalTrials.gov processed this record on September 22, 2014