- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01411410
Phase I Study of PI3(Phosphoinositol 3)-Kinase Inhibitor BAY80-6946 With Paclitaxel in Patients With Advanced Cancer
A Phase 1 Study of BAY80-6946 (Phosphatidylinositol 3΄-Kinase Inhibitor) in Combination With Paclitaxel in Subjects With Advanced Solid Malignancy
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Missouri
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Saint Louis, Missouri, United States, 63110
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New York
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New York, New York, United States, 10065
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Texas
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Houston, Texas, United States, 77030
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
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
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
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose, measured by adverse event profile
Time Frame: Up to 3 years or longer if indicated
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Up to 3 years or longer if indicated
|
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Adverse event collection
Time Frame: Up to 3 years or longer if indicated
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Up to 3 years or longer if indicated
|
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Pharmacokinetics characterized by Cmax of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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Cmax: maximum drug concentration in plasma after single dose administration
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by Cmax/D of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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Cmax/D: Cmax divided by total dose in [mg]
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by tmax of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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tmax: time to reach maximum drug concentration in plasma after single (first) dose
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by AUC(0-tlast) of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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AUC(0-tlast): AUC from time 0 to the last data point above lower limit of quantification
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by AUC (if possible) of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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AUC: area under the plasma concentration vs time curve from zero to infinity
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by AUC/D of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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AUC/D: AUC divided by total dose in [mg]
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by half-life of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
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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
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AUC(0-25): area under the plasma concentration vs time curve from zero to 25 h p.a.
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by clearance of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by volume of distribution of BAY80-6946 (and its metabolite(s), if needed)
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
|
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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
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AE,ur(0-25): amount of drug excreted via urine during the collection interval 0 - 25 h
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by Cmax of Paclitaxel and 6-OH paclitaxel
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by tmax of Paclitaxel and 6-OH paclitaxel
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by AUC(0-t) of Paclitaxel and 6-OH paclitaxel
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by AUC of Paclitaxel and 6-OH paclitaxel
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by half-life of Paclitaxel and 6-OH paclitaxel
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
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Pharmacokinetics characterized by clearance of Paclitaxel and 6-OH paclitaxel
Time Frame: Multiple time points up to 6 weeks
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Multiple time points up to 6 weeks
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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
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Multiple time points up to 6 weeks
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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
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Multiple time points up to 6 weeks
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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
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Multiple time points up to 6 weeks
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Tumor Response as measured by RECIST 1.1 criteria
Time Frame: Up to 3 years or longer if indicated
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Up to 3 years or longer if indicated
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Number of patients with mutational status
Time Frame: Up to 3 years or longer if indicated
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Up to 3 years or longer if indicated
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 12874
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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