Phase I Study of PI3(Phosphoinositol 3)-Kinase Inhibitor... | NCT01411410

NCT01411410

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

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Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	Drug: Paclitaxel Drug: Copanlisib (BAY80-6946)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Paclitaxel	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Adverse event collection		Up to 3 years or longer if indicated
Maximum tolerated dose, measured by adverse event profile		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	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]	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	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	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	Multiple time points up to 6 weeks

Secondary Outcomes

Measure	Description	Time Frame
Number of patients with mutational status		Up to 3 years or longer if indicated
Tumor Response as measured by RECIST 1.1 criteria		Up to 3 years or longer if indicated

Eligibility Module

Eligibility Criteria

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.

Facility	Status	City	State	ZIP	Country	Contacts
		St Louis	Missouri	63110	United States

ID	Term
D017239	Paclitaxel
C000589253	copanlisib

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic