Neoplasms
Conditions
Keywords
Regorafenib, Probe substrates, Pharmacokinetics, Cancer, Safety, Advanced solid malignant tumors
Brief 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
Interventions
DRUGDigoxin
Single dose of digoxin 0.5 mg (2 tablets 0.25 mg) orally without and with regorafenib
DRUGRosuvastatin
Single dose of rosuvastatin 5mg (1 tablet 5 mg) without and with regorafenib 160 mg q.d. (4 tablets 40 mg)
DRUGRegorafenib (Stivarga, BAY73-4506)
Once daily orally 160 mg (4 tablets 40 mg)
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)) for Digoxin | On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15 |
| Maximum drug concentration (Cmax) in plasma for Digoxin | 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 | On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15 |
| Maximum drug concentration (Cmax) in plasma for rosuvastatin | On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15 |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with adverse events as a measure of safety and tolerability | Up to 30 days after last dose |
| Number of participants with drug related adverse events as a measure of safety and tolerability | Up to 30 days after last dose |
| Tumor Response following RECIST criteria | From first dose up to 3 months after end of treatment |
Countries
Germany, Hungary
Outcome results
None listed