Clinical trial NCT02106845: Effect of Regorafenib on Digoxin and Rosuvastatin in Patients With Advanced Solid Malignant Tumors.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Regorafenib
Probe substrates
Pharmacokinetics
Cancer
Safety
Advanced solid malignant tumors
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2014-04-08
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)) for Digoxin
timeFrame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
measure: Maximum drug concentration (Cmax) in plasma for Digoxin
timeFrame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
measure: Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)) for rosuvastatin
timeFrame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
measure: Maximum drug concentration (Cmax) in plasma for rosuvastatin
timeFrame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
Secondary outcomes:
measure: Tumor Response following RECIST criteria
timeFrame: From first dose up to 3 months after end of treatment
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Up to 30 days after last dose
measure: Number of participants with drug related adverse events as a measure of safety and tolerability
timeFrame: Up to 30 days after last dose
Other outcomes:
Locations:
city: Freiburg
country: Germany
state: Baden-Württemberg
city: Frankfurt
country: Germany
state: Hessen
city: Herne
country: Germany
state: Nordrhein-Westfalen
city: Budapest
country: Hungary
city: Budapest
country: Hungary
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: