NeoplasmsPhase 1NCT01287598
BAY73-4506 Probe Substrate Study
A Phase 1 study testing Regorafenib (Stivarga, BAY73-4506), Warfarin and Omeprazole in people with Neoplasms, run by Bayer at 4 sites in Canada.
Trial summary
To evaluate the effect of BAY73-4506 on the pharmacokinetics of probe substrates of CYP 2C9 (warfarin), 2C19 (omeprazole) and 3A4 (midazolam) administered in a cocktail approach and on the pharmacokinetics of a probe substrate of CYP 2C8 (rosiglitazone) To evaluate safety, anti-tumor activity, pharmacokinetics, and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Regorafenib (Stivarga, BAY73-4506), Warfarin and Omeprazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 4 sitesCanada
- Study dates
- 2 Aug 2011to 30 Jul 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
- Female and male subjects must be ≥ 18 years at the first screening examination / visit
- ECOG Performance Status of ≤ 2
- Histological or cytological documentation of confirmed advanced solid tumors. Subjects should have measurable or non-measurable disease according to RECIST
- Life Expectancy of at least 3 months
- Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements conducted within 14 days prior to the first study treatment:
- Hemoglobin ≥ 9.0 g/dL
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- Absolute neutrophil count (ANC) ≥1,500/mm3
- Platelet count ≥ 100,000/ mm3
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2 times ULN
- ALT and AST ≤ 2.5 x ULN (≤ 5.0 x ULN for subjects with cancer involving the liver)
- Serum creatinine ≤ 1.5 times ULN and glomerular filtration rate (GFR)≥ 30 ml/min/1.73 m2, according to the MDRD (Modified Diet in Renal Disease) abbreviated formula
- Lipase ≤ 1.5 ULN
- INR and PTT ≤ 1.5 ULN
- Subjects who are therapeutically treated with warfarin, heparin or other anticoagulants are not eligible for study participation in Group A. Subjects who are therapeutically treated with warfarin, heparin or other anticoagulants, will be allowed to participate in Group B of the study provided they meet all eligibility criteria. Close monitoring of at least weekly evaluations will be performed until INR or PTT are stable by the local standard of care.
- Recovery from previous drug/procedure-related toxicities to CTC Grade 0 or 1 levels (except for alopecia), or to baseline preceding the prior treatment. Preexisting chemotherapy induced sensory neuropathy of CTC Grade ≤2 is not an exclusion criteria.
- Negative serum pregnancy test must be obtained within 7 days prior to the start of treatment in women of childbearing potential. Negative results must be available prior to study treatment.
- Subjects enrolled in this study must use adequate barrier birth control measures prior to, during the course of the study, and 3 months after the last administration of regorafenib.
- An adequate contraception includes the use of condoms or a vasectomy, hormonal contraception with implants or combined PO contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy. In addition, adequate birth control measures for the subject's partner is required, such as a hormonal contraception with implants or combined PO contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy, use of condoms or a vasectomy.
Who cannot join
- History of cardiac disease: Congestive heart failure (New York Heart Association, NYHA, Class III or IV) or active coronary artery disease (unstable angina [angina symptoms at rest] or new-onset angina [began within the last 3 months] or myocardial infarction within the past 6 months). Treatment with Type 1A or 3 anti-arrhythmics, such as Quinidine, Procainamide, Amiodarone, or Sotalol are not permitted. β-Blockers and digoxin are permitted.
- Left ventricular ejection fraction (LVEF) < 50% or below the LLN for the institution (whichever is higher).
- Subjects with pheochromocytoma
- Dehydration NCI-CTCAE, version 4, Grade > 1
- Uncontrolled hypertension (failure of diastolic blood pressure to fall to or below 90 mmHg or systolic blood pressure to fall to or below 140 mmHg with or without the use of antihypertensive drugs). At screening, subjects with history of hypertension should be on a stable anti-hypertensive treatment for at least 7 days prior to the first dose of study drug.
- Patients with known allergy to any of the study drug(s) to be administered, including known severe allergies, non-allergic drug reactions, or multiple drug allergies to any of the study drug(s) to be administered. This is also includes hypersensitivity to any of the compounds or excipients that will be administered to the study subject, specifically regorafenib, and warfarin, omeprazole and midazolam for subjects in Group A, or rosiglitazone for subjects in Group B.
- Subjects with arterial or venous thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism within 6 months before the start of study medication.
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2
Sir Mortimer B. Davis Jewish General Hospital
Montreal, Quebec, H3T 1E2
British Columbia Cancer Agency-Vancouver Centre
Vancouver, British Columbia, V5Z 4E6
About this study
Official title: A Phase I, Non-randomized Open-label Study to Evaluate the Effect of BAY73-4506 (Regorafenib) on Probe Substrates of CYP 2C9 (Warfarin), 2C19 (Omeprazole) and 3A4 (Midazolam) in a Cocktail Approach (Group A) and on a Probe Substrate of CYP 2C8 (Rosiglitazone, Group B) in Patients With Advanced Solid Tumors
- To evaluate the effect of BAY73-4506 on the pharmacokinetics of probe substrates of CYP 2C9 (warfarin), 2C19 (omeprazole) and 3A4 (midazolam) administered in a cocktail approach and on the pharmacokinetics of a probe substrate of CYP 2C8 (rosiglitazone)
- To evaluate safety, anti-tumor activity, pharmacokinetics, and pharmacodynamics of BAY73-4506 in patients with advanced solid tumors
- Conditions
- Neoplasms
- Being tested
- Regorafenib (Stivarga, BAY73-4506), Warfarin, Omeprazole, Midazolam, Rosiglitazone
- Keywords
- Phase I, Probe substrate, target therapy, small molecule, pharmacokinetics
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Regorafenib (Stivarga, BAY73-4506)Drug
BAY73-4506 administered once a daily (od) in a 21-day on / 7-day off schedule
WarfarinDrug
CYP 2C9 (warfarin) at Cycle 1
OmeprazoleDrug
CYP 2C19 (omeprazole) at Cycle 1
MidazolamDrug
CYP 3A4 (midazolam) at Cycle 1
RosiglitazoneDrug
CYP2C8 (rosiglitazone) at Cycle 1
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Regorafenib (Stivarga, BAY73-4506) + warfarin + omeprazole + midazolam Receives: Drug: Regorafenib (Stivarga, BAY73-4506); Drug: Warfarin; Drug: Omeprazole; Drug: Midazolam |
| Arm 2 | Experimental | Regorafenib (Stivarga, BAY73-4506) + rosiglitazone Receives: Drug: Regorafenib (Stivarga, BAY73-4506); Drug: Rosiglitazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of probe substrates (AUC, Cmax, etc.)
Measured: Approximately 6 weeks
Secondary outcomes (2)
Tumor Response evaluation measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Measured: Up to 3 years or longer if indicated
Adverse event collection
Measured: Up to 3 years or longer if indicated
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2011 (estimated)
- Study start2 Aug 2011
- Primary completion3 Jul 2018
- Study completion30 Jul 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 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
- NCT01287598
- Sponsor's protocol ID
- 12434
- Status last verified
- Jul 2019
- First submitted
- 31 Jan 2011
- Last updated
- 10 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Non-randomized Open-label Study to Evaluate the Effect of BAY73-4506 (Regorafenib) on Probe Substrates of CYP 2C9 (Warfarin), 2C19 (Omeprazole) and 3A4 (Midazolam) in a Cocktail Approach (Group A) and on a Probe Substrate of CYP 2C8 (Rosiglitazone, Group B) in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01287598
- Acronym / sponsor ID
- 12434
- Conditions
- Neoplasms
- Keywords
- Phase I, Probe substrate, target therapy, small molecule, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 2 Aug 2011 (actual)
- Primary completion
- 3 Jul 2018 (actual)
- Study completion
- 30 Jul 2018 (actual)
- First posted
- 1 Feb 2011 (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.
- To evaluate the effect of BAY73-4506 on the pharmacokinetics of probe substrates of CYP 2C9 (warfarin), 2C19 (omeprazole) and 3A4 (midazolam) administered in a cocktail approach and on the pharmacokinetics of a probe substrate of CYP 2C8 (rosiglitazone)
- To evaluate safety, anti-tumor activity, pharmacokinetics, and pharmacodynamics of BAY73-4506 in patients with advanced solid tumors
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Regorafenib (Stivarga, BAY73-4506), Drug: Warfarin, Drug: Omeprazole, Drug: MidazolamRegorafenib (Stivarga, BAY73-4506) + warfarin + omeprazole + midazolam |
| Arm 2 | Experimental | Drug: Regorafenib (Stivarga, BAY73-4506), Drug: RosiglitazoneRegorafenib (Stivarga, BAY73-4506) + rosiglitazone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Female and male subjects must be ≥ 18 years at the first screening examination / visit
- ECOG Performance Status of ≤ 2
- Histological or cytological documentation of confirmed advanced solid tumors. Subjects should have measurable or non-measurable disease according to RECIST
- Life Expectancy of at least 3 months
- Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements conducted within 14 days prior to the first study treatment:
Key exclusion criteria (7 listed)
- History of cardiac disease: Congestive heart failure (New York Heart Association, NYHA, Class III or IV) or active coronary artery disease (unstable angina [angina symptoms at rest] or new-onset angina [began within the last 3 months] or myocardial infarction within the past 6 months). Treatment with Type 1A or 3 anti-arrhythmics, such as Quinidine, Procainamide, Amiodarone, or Sotalol are not permitted. β-Blockers and digoxin are permitted.
- Left ventricular ejection fraction (LVEF) < 50% or below the LLN for the institution (whichever is higher).
- Subjects with pheochromocytoma
- Dehydration NCI-CTCAE, version 4, Grade > 1
- Uncontrolled hypertension (failure of diastolic blood pressure to fall to or below 90 mmHg or systolic blood pressure to fall to or below 140 mmHg with or without the use of antihypertensive drugs). At screening, subjects with history of hypertension should be on a stable anti-hypertensive treatment for at least 7 days prior to the first dose of study drug.
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 |
|---|---|---|
| Regorafenib (Stivarga, BAY73-4506)BAY73-4506 administered once a daily (od) in a 21-day on / 7-day off schedule | Drug | Arm 1, Arm 2 |
| WarfarinCYP 2C9 (warfarin) at Cycle 1 | Drug | Arm 1 |
| OmeprazoleCYP 2C19 (omeprazole) at Cycle 1 | Drug | Arm 1 |
| MidazolamCYP 3A4 (midazolam) at Cycle 1 | Drug | Arm 1 |
| RosiglitazoneCYP2C8 (rosiglitazone) at Cycle 1 | Drug | Arm 2 |
Primary outcome
Pharmacokinetics of probe substrates (AUC, Cmax, etc.)
Time frame: Approximately 6 weeks
2 secondary outcomes
Tumor Response evaluation measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time frame: Up to 3 years or longer if indicated
Adverse event collection
Time frame: Up to 3 years or longer if indicated
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 10 Jul 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
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Regorafenib (Stivarga, BAY73-4506), Warfarin and Omeprazole in people with Neoplasms, run by Bayer at 4 sites in Canada.
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 19 inclusion and 7 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 10 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. 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?
Pharmacokinetics of probe substrates (AUC, Cmax, etc.) (time frame: Approximately 6 weeks). 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 10 Jul 2019.