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

NCT02106845 | Completed Phase 1

• 2 other identifiers: 166742013-003613-18
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 5

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

Conditions

Neoplasms

Keywords

Regorafenib; Probe substrates; Pharmacokinetics; Cancer; Safety; Advanced solid malignant tumors

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• Tumor Response following RECIST criteria

  From first dose up to 3 months after end of treatment

• 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

Study Arms (2)

P-gp probe substrate(digoxin)+regorafenib

EXPERIMENTAL

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

Group B: BCRP probe substrate (rosuvastatin) + regorafenib

EXPERIMENTAL

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

Interventions

Digoxin DRUG

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

P-gp probe substrate(digoxin)+regorafenib

Rosuvastatin DRUG

Single dose of rosuvastatin 5mg (1 tablet 5 mg) without and with regorafenib 160 mg q.d. (4 tablets 40 mg)

Group B: BCRP probe substrate (rosuvastatin) + regorafenib

Regorafenib (Stivarga, BAY73-4506) DRUG

Once daily orally 160 mg (4 tablets 40 mg)

Group B: BCRP probe substrate (rosuvastatin) + regorafenib; P-gp probe substrate(digoxin)+regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Potassium, magnesium and calcium blood levels within normal range according to the local laboratory.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (5)

Unknown Facility

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Unknown Facility

Frankfurt am Main, Hesse, 60488, Germany

Location

Unknown Facility

Herne, North Rhine-Westphalia, 44625, Germany

Location

Unknown Facility

Budapest, 1083, Hungary

Location

Unknown Facility

Budapest, 1122, Hungary

Location

Related Links

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

MeSH Terms

Conditions

Neoplasms

Interventions

Digoxin; Rosuvastatin Calcium; regorafenib

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2014
• First Posted: April 8, 2014
• Study Start: April 22, 2014
• Primary Completion: April 27, 2015
• Study Completion: June 12, 2018
• Last Updated: June 7, 2019

Record last verified: 2019-06

Locations

DE (3); HU (2)