NeoplasmsPhase 1NCT01411410
Phase I Study of PI3(Phosphoinositol 3)-Kinase Inhibitor BAY80-6946 With Paclitaxel in Patients With Advanced Cancer
A Phase 1 study testing Paclitaxel and Copanlisib (BAY80-6946) in people with Neoplasms, run by Bayer at 3 sites in United States.
Trial summary
This open label Phase 1 study involves treating subjects with advanced cancer with BAY80-6946 in combination with paclitaxel. It will determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of BAY80-6946 in combination with paclitaxel. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Paclitaxel and Copanlisib (BAY80-6946)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 3 sitesUnited States
- Study dates
- 24 Aug 2011to 29 Jun 2015
- 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
- Subjects must have defined tumor classification (ie, TNBC, HER2+ or Luminal) for enrollment. If tumor classification is not available the subject cannot be enrolled. Tumor classification can be based on analysis of archived tumor tissue, or analysis of tumor tissue collected at any time proximal to screening. Subject profile can also be derived from analysis of fresh tumor tissue obtained during screening. Shipment of specimens (archival or fresh tumor tissue, blood, and plasma) to a central lab can take place after subject enrollment.
- No prior paclitaxel treatment for subjects in the dose escalation phase. MTD cohort expansion subjects may have had prior paclitaxel, but must not have experienced moderate or severe hypersensitivity reactions to the drug. Peripheral neuropathy must be Grade ≤ 1.
- Histological or cytological documentation of non-hematologic malignant solid tumor, excluding primary brain or spinal tumors. Patients with prior central nervous system metastases are eligible if all of the following apply: -- Definitive treatment for all lesions (eg, surgery, radiation) was completed at least three months prior to enrollment -- All lesions must be stable or improving on MRI scan performed within one month of enrollment -- All symptoms of the prior CNS metastases are stable.
- At least one measurable lesion or evaluable disease, as per RECIST 1.1
- ECOG Performance Status Assessment of 0 or 1
- Life expectancy of at least 12 weeks
Show all 17Show fewer
- Exclusion Criteria:- History of moderate to severe hypersensitivity (allergy) to drugs formulated in Cremophor® EL (polyoxyethylated castor oil), such as vitamin K, cyclosporin for injection concentrate and teniposide for injection concentrate
- Pre-existing interstitial lung disease and/or severe impaired pulmonary function
- History of cardiac disease; congestive heart failure (CHF) >NYHA Class II; active coronary artery disease, myocardial infarction within 6 months prior to study entry; new onset angina within 3 months prior to study entry or unstable angina, or ventricular cardiac arrhythmias requiring anti-arrhythmic therapy
- Prior diagnosis of Type 1 or 2 diabetes mellitus, hyperglycemia (defined as consistent fasting blood or plasma glucose > 125 mg/dL) or HgBA1c ≥ 7%
- Active clinically serious infections Grade ≥ 2 (NCI-CTCAE version 4.0), including viral hepatitis
- Poorly controlled seizure disorder
- Poorly controlled hypertension, defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis C or B
- Subjects undergoing renal dialysis
- Known bleeding diathesis
- Pregnant or breast feeding women.
Who cannot join
None listed.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Study site
Houston, Texas, 77030
Study site
New York, New York, 10065
Study site
St Louis, Missouri, 63110
About this study
Official title: A Phase 1 Study of BAY80-6946 (Phosphatidylinositol 3΄-Kinase Inhibitor) in Combination With Paclitaxel in Subjects With Advanced Solid Malignancy
This open label Phase 1 study involves treating subjects with advanced cancer with BAY80-6946 in combination with paclitaxel. It will determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of BAY80-6946 in combination with paclitaxel. The trial will involve multiple participating sites from the US. Following determination of the MTD, an expansion cohort of 20 evaluable subjects with breast cancer was planned. Finally, 16 patients have been enrolled to treatment (Cohort 3). A new expansion cohort with modified dosing cohort is now introduced (Cohort 4: breast cancer expansion cohort with modified dosing) in which another 20 subjects are planned to be enrolled to treatment.
- Conditions
- Neoplasms
- Being tested
- Paclitaxel, Copanlisib (BAY80-6946)
- Keywords
- phase I, phosphatidylinositol 3΄-kinase (PI3K), paclitaxel, Maximum tolerated Dose
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaclitaxelDrug
Paclitaxel (80 mg/m2 in Cohort 1, 2 and 3, 90 mg/m2 in Cohort 4) as 60-minute iv infusion once weekly on Days 1, 8, 15 and 22 (Day 22 in Cohort 1, 2 and 3 only) in 28-day cycles
- The following intravenous premedications are required 30 to 60 minutes before paclitaxel infusion: Dexamethasone (10 mg), diphenhydramine (50 mg) and either cimetidine (300 mg) or ranitidine (50 mg)
- Alternatively, for premedications other than dexamethasone, the standard institutional regimen is permitted.
Copanlisib (BAY80-6946)Drug
BAY80-6946 (0.6 mg/kg in Cohort 1, 0.8 mg/kg in Cohort 2, 3 and 4) as 60-minute iv infusion once weekly on Days 2, 9, 16 and 23 (Day 23 in Cohort 1, 2 and 3 only) in 28-day cycles
| Study group | Role | What they receive |
|---|---|---|
| Copanlisib (BAY80-6946) | Experimental | The treatment of consists of repetitive cycles, each over 4 weeks. It continues until disease progression or limiting toxicity. If paclitaxel is discontinued for toxicity, BAY80-6946 may continue at the discretion of the investigator if a clinical benefit (response or stable disease for 6 months) is noted. Receives: Drug: Paclitaxel; Drug: Copanlisib (BAY80-6946) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event collection
Measured: Up to 3 years or longer if indicated
Maximum tolerated dose, measured by adverse event profile
Measured: Up to 3 years or longer if indicated
Pharmacokinetics characterized by Cmax of BAY80-6946 (and its metabolite(s), if needed)
Cmax: maximum drug concentration in plasma after single dose administration
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by Cmax/D of BAY80-6946 (and its metabolite(s), if needed)
Cmax/D: Cmax divided by total dose in [mg]
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by tmax of BAY80-6946 (and its metabolite(s), if needed)
tmax: time to reach maximum drug concentration in plasma after single (first) dose
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC(0-tlast) of BAY80-6946 (and its metabolite(s), if needed)
AUC(0-tlast): AUC from time 0 to the last data point above lower limit of quantification
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC (if possible) of BAY80-6946 (and its metabolite(s), if needed)
AUC: area under the plasma concentration vs time curve from zero to infinity
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC/D of BAY80-6946 (and its metabolite(s), if needed)
AUC/D: AUC divided by total dose in [mg]
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by half-life of BAY80-6946 (and its metabolite(s), if needed)
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by partial AUC values [eg, AUC(0-25)] of BAY80-6946 (and its metabolite(s), if needed)
AUC(0-25): area under the plasma concentration vs time curve from zero to 25 h p.a.
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by clearance of BAY80-6946 (and its metabolite(s), if needed)
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by volume of distribution of BAY80-6946 (and its metabolite(s), if needed)
Measured: Multiple time points up to 6 weeks
Estimation of percent of dose excreted [unchanged or as metabolites, if relevant) renally during 0 - 25 h after start of BAY80-6946 infusion (AE,ur(0-25)] (for Cohort 4 only)
AE,ur(0-25): amount of drug excreted via urine during the collection interval 0 - 25 h
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by Cmax of Paclitaxel and 6-OH paclitaxel
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by tmax of Paclitaxel and 6-OH paclitaxel
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC(0-t) of Paclitaxel and 6-OH paclitaxel
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC of Paclitaxel and 6-OH paclitaxel
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by half-life of Paclitaxel and 6-OH paclitaxel
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by clearance of Paclitaxel and 6-OH paclitaxel
Measured: Multiple time points up to 6 weeks
Pharmacokinetics characterized by volume of distribution (If possible and needed) of Paclitaxel and 6-OH paclitaxel
Measured: Multiple time points up to 6 weeks
Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing Cmax of Cycle 1 Day 1 and Cycle 1 Day 15
Measured: Multiple time points up to 6 weeks
Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing AUC(0-tlast) of Cycle 1 Day 1 and Cycle 1 Day 15
Measured: Multiple time points up to 6 weeks
Secondary outcomes (2)
Number of patients with mutational status
Measured: Up to 3 years or longer if indicated
Tumor Response as measured by RECIST 1.1 criteria
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 posted8 Aug 2011 (estimated)
- Study start24 Aug 2011
- Primary completion22 Oct 2014
- Study completion29 Jun 2015
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 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
- NCT01411410
- Sponsor's protocol ID
- 12874
- Status last verified
- Oct 2017
- First submitted
- 5 Aug 2011
- Last updated
- 11 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of BAY80-6946 (Phosphatidylinositol 3΄-Kinase Inhibitor) in Combination With Paclitaxel in Subjects With Advanced Solid Malignancy
- ClinicalTrials.gov ID
- NCT01411410
- Acronym / sponsor ID
- 12874
- Conditions
- Neoplasms
- Keywords
- phase I, phosphatidylinositol 3΄-kinase (PI3K), paclitaxel, Maximum tolerated Dose
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 24 Aug 2011 (actual)
- Primary completion
- 22 Oct 2014 (actual)
- Study completion
- 29 Jun 2015 (actual)
- First posted
- 8 Aug 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.
This open label Phase 1 study involves treating subjects with advanced cancer with BAY80-6946 in combination with paclitaxel. It will determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D) of BAY80-6946 in combination with paclitaxel. The trial will involve multiple participating sites from the US. Following determination of the MTD, an expansion cohort of 20 evaluable subjects with breast cancer was planned. Finally, 16 patients have been enrolled to treatment (Cohort 3). A new expansion cohort with modified dosing cohort is now introduced (Cohort 4: breast cancer expansion cohort with modified dosing) in which another 20 subjects are planned to be enrolled to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Copanlisib (BAY80-6946) | Experimental | Drug: Paclitaxel, Drug: Copanlisib (BAY80-6946)The treatment of consists of repetitive cycles, each over 4 weeks. It continues until disease progression or limiting toxicity. If paclitaxel is discontinued for toxicity, BAY80-6946 may continue at the discretion of the investigator if a clinical benefit (response or stable disease for 6 months) is noted. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Subjects must have defined tumor classification (ie, TNBC, HER2+ or Luminal) for enrollment. If tumor classification is not available the subject cannot be enrolled. Tumor classification can be based on analysis of archived tumor tissue, or analysis of tumor tissue collected at any time proximal to screening. Subject profile can also be derived from analysis of fresh tumor tissue obtained during screening. Shipment of specimens (archival or fresh tumor tissue, blood, and plasma) to a central lab can take place after subject enrollment.
- No prior paclitaxel treatment for subjects in the dose escalation phase. MTD cohort expansion subjects may have had prior paclitaxel, but must not have experienced moderate or severe hypersensitivity reactions to the drug. Peripheral neuropathy must be Grade ≤ 1.
- Histological or cytological documentation of non-hematologic malignant solid tumor, excluding primary brain or spinal tumors. Patients with prior central nervous system metastases are eligible if all of the following apply: -- Definitive treatment for all lesions (eg, surgery, radiation) was completed at least three months prior to enrollment -- All lesions must be stable or improving on MRI scan performed within one month of enrollment -- All symptoms of the prior CNS metastases are stable.
- At least one measurable lesion or evaluable disease, as per RECIST 1.1
- ECOG Performance Status Assessment of 0 or 1
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| PaclitaxelPaclitaxel (80 mg/m2 in Cohort 1, 2 and 3, 90 mg/m2 in Cohort 4) as 60-minute iv infusion once weekly on Days 1, 8, 15 and 22 (Day 22 in Cohort 1, 2 and 3 only) in 28-day cycles * The following intravenous premedications are required 30 to 60 minutes before paclitaxel infusion: Dexamethasone (10 mg), diphenhydramine (50 mg) and either cimetidine (300 mg) or ranitidine (50 mg) * Alternatively, for premedications other than dexamethasone, the standard institutional regimen is permitted. | Drug | Copanlisib (BAY80-6946) |
| Copanlisib (BAY80-6946)BAY80-6946 (0.6 mg/kg in Cohort 1, 0.8 mg/kg in Cohort 2, 3 and 4) as 60-minute iv infusion once weekly on Days 2, 9, 16 and 23 (Day 23 in Cohort 1, 2 and 3 only) in 28-day cycles | Drug | Copanlisib (BAY80-6946) |
Primary outcome
Adverse event collection
Time frame: Up to 3 years or longer if indicated
Maximum tolerated dose, measured by adverse event profile
Time frame: Up to 3 years or longer if indicated
Pharmacokinetics characterized by Cmax of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
Cmax: maximum drug concentration in plasma after single dose administration
Pharmacokinetics characterized by Cmax/D of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
Cmax/D: Cmax divided by total dose in [mg]
Pharmacokinetics characterized by tmax of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
tmax: time to reach maximum drug concentration in plasma after single (first) dose
Pharmacokinetics characterized by AUC(0-tlast) of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
AUC(0-tlast): AUC from time 0 to the last data point above lower limit of quantification
Pharmacokinetics characterized by AUC (if possible) of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
AUC: area under the plasma concentration vs time curve from zero to infinity
Pharmacokinetics characterized by AUC/D of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
AUC/D: AUC divided by total dose in [mg]
Pharmacokinetics characterized by half-life of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
Pharmacokinetics characterized by partial AUC values [eg, AUC(0-25)] of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
AUC(0-25): area under the plasma concentration vs time curve from zero to 25 h p.a.
Pharmacokinetics characterized by clearance of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
Pharmacokinetics characterized by volume of distribution of BAY80-6946 (and its metabolite(s), if needed)
Time frame: Multiple time points up to 6 weeks
Estimation of percent of dose excreted [unchanged or as metabolites, if relevant) renally during 0 - 25 h after start of BAY80-6946 infusion (AE,ur(0-25)] (for Cohort 4 only)
Time frame: Multiple time points up to 6 weeks
AE,ur(0-25): amount of drug excreted via urine during the collection interval 0 - 25 h
Pharmacokinetics characterized by Cmax of Paclitaxel and 6-OH paclitaxel
Time frame: Multiple time points up to 6 weeks
Pharmacokinetics characterized by tmax of Paclitaxel and 6-OH paclitaxel
Time frame: Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC(0-t) of Paclitaxel and 6-OH paclitaxel
Time frame: Multiple time points up to 6 weeks
Pharmacokinetics characterized by AUC of Paclitaxel and 6-OH paclitaxel
Time frame: Multiple time points up to 6 weeks
Pharmacokinetics characterized by half-life of Paclitaxel and 6-OH paclitaxel
Time frame: Multiple time points up to 6 weeks
Pharmacokinetics characterized by clearance of Paclitaxel and 6-OH paclitaxel
Time frame: Multiple time points up to 6 weeks
Pharmacokinetics characterized by volume of distribution (If possible and needed) of Paclitaxel and 6-OH paclitaxel
Time frame: Multiple time points up to 6 weeks
Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing Cmax of Cycle 1 Day 1 and Cycle 1 Day 15
Time frame: Multiple time points up to 6 weeks
Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing AUC(0-tlast) of Cycle 1 Day 1 and Cycle 1 Day 15
Time frame: Multiple time points up to 6 weeks
2 secondary outcomes
Number of patients with mutational status
Time frame: Up to 3 years or longer if indicated
Tumor Response as measured by RECIST 1.1 criteria
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 11 Oct 2017.
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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
3 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 Paclitaxel and Copanlisib (BAY80-6946) in people with Neoplasms, run by Bayer at 3 sites in United States.
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 17 inclusion and 0 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 11 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
Adverse event collection (time frame: Up to 3 years or longer if indicated). The study lists 22 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 11 Oct 2017.