Effect of Regorafenib on Digoxin and Rosuvastatin in Patients With Advanced Solid Malignant Tumors.
- Conditions
- Neoplasms
- Interventions
- Registration Number
- NCT02106845
- Lead Sponsor
- Bayer
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
-
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.
-
For ALL patients
-
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication.
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Non-healing wound, skin ulcer, or bone fracture.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Group B: BCRP probe substrate (rosuvastatin) + regorafenib Regorafenib (Stivarga, BAY73-4506) - P-gp probe substrate(digoxin)+regorafenib Regorafenib (Stivarga, BAY73-4506) - P-gp probe substrate(digoxin)+regorafenib Digoxin - Group B: BCRP probe substrate (rosuvastatin) + regorafenib Rosuvastatin -
- Primary Outcome Measures
Name Time Method Maximum drug concentration (Cmax) in plasma for rosuvastatin 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 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
- Secondary Outcome Measures
Name Time Method Number of participants with drug related adverse events as a measure of safety and tolerability Up to 30 days after last dose Number of participants with 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