NeoplasmsPhase 1NCT02106845
Effect of Regorafenib on Digoxin and Rosuvastatin in Patients With Advanced Solid Malignant Tumors.
A Phase 1 study testing Digoxin, Rosuvastatin and Regorafenib (Stivarga, BAY73-4506) in people with Neoplasms, run by Bayer at 5 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Digoxin, Rosuvastatin and Regorafenib (Stivarga, BAY73-4506)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 22 Apr 2014to 12 Jun 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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 locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Germany3 sites
Study site
Frankfurt am Main, Hesse, 60488
Study site
Freiburg im Breisgau, Baden-Wurttemberg, 79106
Study site
Herne, North Rhine-Westphalia, 44625
About this study
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
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
- Being tested
- Digoxin, Rosuvastatin, Regorafenib (Stivarga, BAY73-4506)
- Keywords
- Regorafenib, Probe substrates, Pharmacokinetics, Cancer, Safety, Advanced solid malignant tumors
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DigoxinDrug
Single dose of digoxin 0.5 mg (2 tablets 0.25 mg) orally without and with regorafenib
RosuvastatinDrug
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)Drug
Once daily orally 160 mg (4 tablets 40 mg)
| Study group | Role | What they receive |
|---|---|---|
| P-gp probe substrate(digoxin)+regorafenib | Experimental | Not described Receives: Drug: Digoxin; Drug: Regorafenib (Stivarga, BAY73-4506) |
| Group B: BCRP probe substrate (rosuvastatin) + regorafenib | Experimental | Not described Receives: Drug: Rosuvastatin; Drug: Regorafenib (Stivarga, BAY73-4506) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)) for Digoxin
Measured: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
Maximum drug concentration (Cmax) in plasma for Digoxin
Measured: 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
Measured: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
Maximum drug concentration (Cmax) in plasma for rosuvastatin
Measured: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
Secondary outcomes (3)
Tumor Response following RECIST criteria
Measured: From first dose up to 3 months after end of treatment
Number of participants with adverse events as a measure of safety and tolerability
Measured: Up to 30 days after last dose
Number of participants with drug related adverse events as a measure of safety and tolerability
Measured: Up to 30 days after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study start22 Apr 2014
- Primary completion27 Apr 2015
- Study completion12 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02106845
- Sponsor's protocol ID
- 16674
- Other IDs
- 2013-003613-18
- Status last verified
- Jun 2019
- First submitted
- 4 Apr 2014
- Last updated
- 7 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02106845
- Acronym / sponsor ID
- 16674
- Conditions
- Neoplasms
- Keywords
- Regorafenib, Probe substrates, Pharmacokinetics, Cancer, Safety, Advanced solid malignant tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 22 Apr 2014 (actual)
- Primary completion
- 27 Apr 2015 (actual)
- Study completion
- 12 Jun 2018 (actual)
- First posted
- 8 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- The following criteria apply to ALL patients starting the study treatment:
- The following inclusion criteria apply to Group A (digoxin + regorafenib) patients ONLY:
- The following inclusion criteria apply to Group B (rosuvastatin + regorafenib) patients ONLY:
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DigoxinSingle dose of digoxin 0.5 mg (2 tablets 0.25 mg) orally without and with regorafenib | Drug | P-gp probe substrate(digoxin)+regorafenib |
| RosuvastatinSingle dose of rosuvastatin 5mg (1 tablet 5 mg) without and with regorafenib 160 mg q.d. (4 tablets 40 mg) | Drug | Group B: BCRP probe substrate (rosuvastatin) + regorafenib |
| Regorafenib (Stivarga, BAY73-4506)Once daily orally 160 mg (4 tablets 40 mg) | Drug | Group B: BCRP probe substrate (rosuvastatin) + regorafenib, P-gp probe substrate(digoxin)+regorafenib |
Primary outcome
Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)) for Digoxin
Time frame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
Maximum drug concentration (Cmax) in plasma for Digoxin
Time frame: 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
Time frame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
Maximum drug concentration (Cmax) in plasma for rosuvastatin
Time frame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15
3 secondary outcomes
Tumor Response following RECIST criteria
Time frame: From first dose up to 3 months after end of treatment
Number of participants with adverse events as a measure of safety and tolerability
Time frame: Up to 30 days after last dose
Number of participants with drug related adverse events as a measure of safety and tolerability
Time frame: Up to 30 days after last dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Digoxin, Rosuvastatin and Regorafenib (Stivarga, BAY73-4506) in people with Neoplasms, run by Bayer at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration-time curve from time zero to 24 hours (AUC(0-24)) for Digoxin (time frame: On Pre-Cycle Day -7 and on Cycle 1 Day15 or Cycle 2 Day 15). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2019.