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

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02106845
• Other study ID #: 16674
• Secondary ID: 2013-003613-18
• Status: Completed
• Phase: Phase 1
• Start date: April 22, 2014
• Est. completion date: June 12, 2018

Study information

• Verified date: June 2019
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 12, 2018
• Est. primary completion date: April 27, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Digoxin
Single dose of digoxin 0.5 mg (2 tablets 0.25 mg) orally without and with regorafenib
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

Germany,  Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Maximum drug concentration (Cmax) in plasma for Digoxin		On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
Primary	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
Primary	Maximum drug concentration (Cmax) in plasma for rosuvastatin		On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
Secondary	Tumor Response following RECIST criteria		From first dose up to 3 months after end of treatment
Secondary	Number of participants with adverse events as a measure of safety and tolerability		Up to 30 days after last dose
Secondary	Number of participants with drug related adverse events as a measure of safety and tolerability		Up to 30 days after last dose

External Links

•   Click here to find results for studies related to Bayer products.