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

Bayer

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: Rosuvastatin; Drug: Digoxin; Drug: Regorafenib (Stivarga, BAY73-4506)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02106845

2013-003613-18 (EudraCT Number)

16674

Details and patient eligibility

About

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

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

P-gp probe substrate(digoxin)+regorafenib

Experimental group

Treatment:

Drug: Regorafenib (Stivarga, BAY73-4506)

Drug: Digoxin

Group B: BCRP probe substrate (rosuvastatin) + regorafenib

Experimental group

Treatment:

Drug: Regorafenib (Stivarga, BAY73-4506)

Drug: Rosuvastatin