NeoplasmsPhase 1NCT01392521
Phase Ib Study of PI3(Phosphoinositol 3)-Kinase Inhibitor Copanlisib With MEK (Mitogen-activated Protein Kinase) Inhibitor Refametinib (BAY86-9766) in Patients With Advanced Cancer
A Phase 1 study testing Copanlisib + Refametinib (BAY86-9766) in people with Neoplasms, run by Bayer at 8 sites in 3 countries.
Trial summary
The PI3K (phosphoinositol 3-Kinase) inhibitor Copanlisib and the MEK (mitogen-activated protein kinase) inhibitor Refametinib (BAY86-9766)have both been tested as single agent treatments in other phase I studies. This study will test the combination of these two drugs to try and answer the following questions: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Copanlisib + Refametinib (BAY86-9766)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 8 sitesin 3 countries
- Study dates
- Jul 2011to Apr 2014
- 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
- Age greater than/equal to 18 years old
- ECOG Performance Status of 0 - 1
- Life expectancy of at least 12 weeks
- Patients with advanced, histologically or cytologically confirmed solid tumors, refractory to any standard therapy or have no standard therapy available
- LVEF (left ventricular ejection fraction) > or = to the lower limit of normal for the institution
- Radiographically or clinically evaluable tumor
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- Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 14 days prior to start of first dose:
- Hemoglobin > 9.0 g/dL
- Absolute neutrophil count (ANC) > or = 1500/mm3
- Platelet count > or = 100,000 /mm3
- Total bilirubin < or = 1.5 times the upper limit of normal
- ALT (alanine aminotransferase) and AST (aspartate aminotransferase) < or = 2.5 x upper limit of normal (< or = 5 x upper limit of normal for patients with liver involvement)
- PT-INR (prothrombin-international normalized ratio) and PTT (partial thromboplastin time) < or = 1.5 times the upper limit of normal
- Serum creatinine < or = 1.5 times the upper limit of normal
Who cannot join
- History of impaired cardiac function or clinically significant cardiac disease (i.e. congestive heart failure (CHF) NYHA (New York Heart Association) Class III or IV); active coronary artery disease, myocardial infarction within 6 months of study entry; new onset or unstable angina within 3 months of study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy
- Type 1 or type 2 diabetes mellitus or fasting glucose > 125 mg/dL or HgBA1c > or = 7.0
- Use of systemic corticosteroids within 2 weeks of study entry
- History of retinal vein occlusion
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- Active clinically serious infection
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- Uncontrolled hypertension
- Positive for HIV, or chronic Hepatitis B or C
- Subjects undergoing renal dialysis
- Known bleeding diathesis
- Ongoing substance abuse
- Pregnant or breast-feeding women
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States6 sites
Study site
Greenville, South Carolina, 29605
Study site
Houston, Texas, 77030
Study site
Las Vegas, Nevada, 89169
Study site
Scottsdale, Arizona, 85260
Study site
Tyler, Texas, 75702
Study site
Vancouver, Washington, 98684
About this study
Official title: Phase Ib Trial of the Combination of PI3K Inhibitor BAY 80-6946 and Allosteric-MEK Inhibitor BAY 86-9766 in Subjects With Advanced Cancer
The PI3K (phosphoinositol 3-Kinase) inhibitor Copanlisib and the MEK (mitogen-activated protein kinase) inhibitor Refametinib (BAY86-9766)have both been tested as single agent treatments in other phase I studies. This study will test the combination of these two drugs to try and answer the following questions:
- What are the side effects of the combination of Copanlisib and Refametinib (BAY86-9766)when given together at different/increasing dose levels?
- What dose level of Copanlisib and Refametinib (BAY86-9766) should be tested in future clinical research studies?
- How much Copanlisib is in the blood at specific times after administration and does adding Refametinib (BAY86-9766) have an affect?
- How much Refametinib (BAY86-9766) is in the blood at specific times after administration and does adding Copanlisib have an affect?
- Does the combination of Refametinib (BAY86-9766) and Copanlisib have an effect on tumors?
- Conditions
- Neoplasms
- Being tested
- Copanlisib + Refametinib (BAY86-9766)
- Keywords
- Safety, Tolerability, Pharmacokinetics
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Copanlisib + Refametinib (BAY86-9766)Drug
Copanlisib will be administered as an IV infusion weekly for 3 weeks in combination with Refametinib (BAY86-9766) at varying dose levels. Refametinib (BAY86-9766) is administered orally twice a day starting at Day 4 of Cycle 1.
Copanlisib + Refametinib (BAY86-9766)Drug
Copanlisib will be administered as an IV infusion weekly in combination with Refametinib (BAY86-9766) at varying dose levels. Refametinib (BAY86-9766) is administered orally twice a day starting at Day 6 of Cycle 1 on a 4 day on, 3 day off schedule.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: Copanlisib + Refametinib (BAY86-9766) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose
Measured: 2 years
Comparison of the Copanlisib AUC when given alone with the AUC when given with Refametinib (BAY86-9766)
Measured: At day 15
Comparison of the Refametinib (BAY86-9766) AUC when given alone with the AUC when given with Copanlisib
Measured: At day 15
Secondary outcomes (4)
Tumor Response as measured by RECIST 1.1 criteria
Measured: 3 years
Biomarker evaluation including analysis of pathway activation in blood and plasma
Measured: 3 years
Tumor Response as measured by FDG-PET at MTD and expansion cohort(s)
Measured: 3 years
Pharmacodynamic biomarker evaluation analysis using paired tumor biopsies
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionFeb 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 64 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
- NCT01392521
- Sponsor's protocol ID
- 12876
- Other IDs
- 2010-024082-45
- Status last verified
- Apr 2015
- First submitted
- 30 Jun 2011
- Last updated
- 17 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Ramanathan RK, Von Hoff DD, Eskens F, Blumenschein G Jr, Richards D, Genvresse I, Reschke S, Granvil C, Skubala A, Pena C, Mross K. Phase Ib Trial of the PI3K Inhibitor Copanlisib Combined with the Allosteric MEK Inhibitor Refametinib in Patients with Advanced Cancer. Target Oncol. 2020 Apr;15(2):163-174. doi: 10.1007/s11523-020-00714-0.
PubMed 32314268
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Trial of the Combination of PI3K Inhibitor BAY 80-6946 and Allosteric-MEK Inhibitor BAY 86-9766 in Subjects With Advanced Cancer
- ClinicalTrials.gov ID
- NCT01392521
- Acronym / sponsor ID
- 12876
- Conditions
- Neoplasms
- Keywords
- Safety, Tolerability, Pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 12 Jul 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.
The PI3K (phosphoinositol 3-Kinase) inhibitor Copanlisib and the MEK (mitogen-activated protein kinase) inhibitor Refametinib (BAY86-9766)have both been tested as single agent treatments in other phase I studies. This study will test the combination of these two drugs to try and answer the following questions:
- What are the side effects of the combination of Copanlisib and Refametinib (BAY86-9766)when given together at different/increasing dose levels?
- What dose level of Copanlisib and Refametinib (BAY86-9766) should be tested in future clinical research studies?
- How much Copanlisib is in the blood at specific times after administration and does adding Refametinib (BAY86-9766) have an affect?
- How much Refametinib (BAY86-9766) is in the blood at specific times after administration and does adding Copanlisib have an affect?
- Does the combination of Refametinib (BAY86-9766) and Copanlisib have an effect on tumors?
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Copanlisib + Refametinib (BAY86-9766) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age greater than/equal to 18 years old
- ECOG Performance Status of 0 - 1
- Life expectancy of at least 12 weeks
- Patients with advanced, histologically or cytologically confirmed solid tumors, refractory to any standard therapy or have no standard therapy available
- LVEF (left ventricular ejection fraction) > or = to the lower limit of normal for the institution
Key exclusion criteria (12 listed)
- History of impaired cardiac function or clinically significant cardiac disease (i.e. congestive heart failure (CHF) NYHA (New York Heart Association) Class III or IV); active coronary artery disease, myocardial infarction within 6 months of study entry; new onset or unstable angina within 3 months of study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy
- Type 1 or type 2 diabetes mellitus or fasting glucose > 125 mg/dL or HgBA1c > or = 7.0
- Use of systemic corticosteroids within 2 weeks of study entry
- History of retinal vein occlusion
- Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
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 |
|---|---|---|
| Copanlisib + Refametinib (BAY86-9766)Copanlisib will be administered as an IV infusion weekly for 3 weeks in combination with Refametinib (BAY86-9766) at varying dose levels. Refametinib (BAY86-9766) is administered orally twice a day starting at Day 4 of Cycle 1. | Drug | Arm 1 |
| Copanlisib + Refametinib (BAY86-9766)Copanlisib will be administered as an IV infusion weekly in combination with Refametinib (BAY86-9766) at varying dose levels. Refametinib (BAY86-9766) is administered orally twice a day starting at Day 6 of Cycle 1 on a 4 day on, 3 day off schedule. | Drug | Arm 1 |
Primary outcome
Maximum Tolerated Dose
Time frame: 2 years
Comparison of the Copanlisib AUC when given alone with the AUC when given with Refametinib (BAY86-9766)
Time frame: At day 15
Comparison of the Refametinib (BAY86-9766) AUC when given alone with the AUC when given with Copanlisib
Time frame: At day 15
4 secondary outcomes
Tumor Response as measured by RECIST 1.1 criteria
Time frame: 3 years
Biomarker evaluation including analysis of pathway activation in blood and plasma
Time frame: 3 years
Tumor Response as measured by FDG-PET at MTD and expansion cohort(s)
Time frame: 3 years
Pharmacodynamic biomarker evaluation analysis using paired tumor biopsies
Time frame: 3 years
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 17 Apr 2015.
- Derived from this study: PubMed 32314268Ramanathan RK, Von Hoff DD, Eskens F, Blumenschein G Jr, Richards D, Genvresse I, Reschke S, Granvil C, Skubala A, Pena C, Mross K. Phase Ib Trial of the PI3K Inhibitor Copanlisib Combined with the Allosteric MEK Inhibitor Refametinib in Patients with Advanced Cancer. Target Oncol. 2020 Apr;15(2):163-174. doi: 10.1007/s11523-020-00714-0.
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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
8 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Copanlisib + Refametinib (BAY86-9766) in people with Neoplasms, run by Bayer at 8 sites in 3 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 14 inclusion and 12 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 17 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Germany, Netherlands. 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?
Maximum Tolerated Dose (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01392521, which also lists 1 linked publication.
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 17 Apr 2015.