Clinical trial NCT01411410: Phase I Study of PI3(Phosphoinositol 3)-Kinase Inhibitor BAY80-6946 With Paclitaxel in Patients With Advanced Cancer
Official title: A Phase 1 Study of BAY80-6946 (Phosphatidylinositol 3΄-Kinase Inhibitor) in Combination With Paclitaxel in Subjects With Advanced Solid Malignancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: phase I
phosphatidylinositol 3΄-kinase (PI3K)
paclitaxel
Maximum tolerated Dose
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2011-08-08
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. 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.


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.

Primary outcomes:
measure: Adverse event collection
timeFrame: Up to 3 years or longer if indicated
measure: Maximum tolerated dose, measured by adverse event profile
timeFrame: Up to 3 years or longer if indicated
measure: Pharmacokinetics characterized by Cmax of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by Cmax/D of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by tmax of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by AUC(0-tlast) of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by AUC (if possible) of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by AUC/D of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by half-life of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by partial AUC values [eg, AUC(0-25)] of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by clearance of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by volume of distribution of BAY80-6946 (and its metabolite(s), if needed)
timeFrame: Multiple time points up to 6 weeks
measure: 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)
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by Cmax of Paclitaxel and 6-OH paclitaxel
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by tmax of Paclitaxel and 6-OH paclitaxel
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by AUC(0-t) of Paclitaxel and 6-OH paclitaxel
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by AUC of Paclitaxel and 6-OH paclitaxel
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by half-life of Paclitaxel and 6-OH paclitaxel
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by clearance of Paclitaxel and 6-OH paclitaxel
timeFrame: Multiple time points up to 6 weeks
measure: Pharmacokinetics characterized by volume of distribution (If possible and needed) of Paclitaxel and 6-OH paclitaxel
timeFrame: Multiple time points up to 6 weeks
measure: Effect of BAY80-6946 on paclitaxel PK will be assessed by comparing Cmax of Cycle 1 Day 1 and Cycle 1 Day 15
timeFrame: Multiple time points up to 6 weeks
measure: 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
timeFrame: Multiple time points up to 6 weeks
Secondary outcomes:
measure: Number of patients with mutational status
timeFrame: Up to 3 years or longer if indicated
measure: Tumor Response as measured by RECIST 1.1 criteria
timeFrame: Up to 3 years or longer if indicated
Other outcomes:
Locations:
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Houston
country: United States
state: Texas
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: