Overview

This trial is active, not recruiting.

Condition neoplasms
Treatments digoxin, rosuvastatin, regorafenib (stivarga, bay73-4506)
Phase phase 1
Sponsor Bayer
Start date April 2014
End date April 2015
Trial size 42 participants
Trial identifier NCT02106845, 16674, 2013-003613-18

Summary

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification pharmacokinetics study
Intervention model crossover assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
digoxin
Single dose of digoxin 0.5 mg (2 tablets 0.25 mg) orally without and with regorafenib
regorafenib (stivarga, bay73-4506)
Once daily orally 160 mg (4 tablets 40 mg)
(Experimental)
rosuvastatin
Single dose of rosuvastatin 5mg (1 tablet 5 mg) without and with regorafenib 160 mg q.d. (4 tablets 40 mg)
regorafenib (stivarga, bay73-4506)
Once daily orally 160 mg (4 tablets 40 mg)

Primary Outcomes

Measure
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 Outcomes

Measure
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

Eligibility Criteria

Male or female participants at least 18 years old.

- 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.

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Bayer.