Clinical trial NCT01188252: Clinical Study to Evaluate the Maximum Tolerated Dose of BAY1000394 Given in a 3 Days on / 4 Days Off Schedule in Subjects With Advanced Malignancies
Official title: An Open-label, Phase I, Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY 1000394 Given Twice Daily in a 3 Days on / 4 Days Off Schedule in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Phase I
Dose escalation
Kinase inhibitor
Cyclin-dependent kinases
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2010-08-25
Enrollment: 112
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: Clinical study to determine safety, tolerability, to measure how the drug is metabolized by the body and to determine the maximum tolerated dose of BAY1000394 given in an intermittent 3 days on / 4 days off schedule to patients with advanced malignancies


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
* Life expectancy of at least 12 weeks
* Subjects with advanced, histologically or cytologically confirmed solid tumors, refractory to any standard therapy, have no standard therapy available, or subjects must have actively refused any treatment which would be regarded standard, and / or if in the judgment of the investigator, experimental treatment is clinically and ethically acceptable
* At least 1 tumor lesion measurable by computer tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST 1.1
* Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements to be conducted within 14 days prior to the first dose of study drug

Exclusion Criteria:

* History of cardiac disease: congestive heart failure \> NYHA Class II, unstable angina (anginal symptoms at rest), any episodes of angina or history of myocardial infarction, cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted), previous venous or arterial thrombotic events, pulmonary embolism
* Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C(3)
* History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
* Active clinically serious infections of CTCAE \> Grade 2 (CTCAE v4.02)
* Symptomatic metastatic brain or meningeal tumors unless the subject is \> 3 months from definitive therapy, has no evidence of tumor growth on an imaging study within 4 weeks prior to study entry, and is clinically stable with respect to the tumor at the time of study entry. Subjects must not be on acute steroid therapy or taper off steroid therapy (chronic steroid therapy is acceptable provided that the dose is stable for 4 weeks prior to study entry and following screening CT / MRI scan). Subjects with neurological symptoms should undergo a CT / MRI scan of the brain to exclude new or progressive brain metastases. Spinal cord metastasis is acceptable
* Seizure disorder requiring therapy (such as steroids or anti-epileptics)
* History of organ allograft
* Evidence or history of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE \> Grade 2 within 4 weeks prior to prior to the first dose of study drug

Primary outcomes:
measure: Safety: Frequency of adverse events
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: Plasma concentrations of BAY1000394 will be measured. The following parameters will be calculated: Cmax, tmax, AUC(0-tn), AUC, and half-life.
timeFrame: Approximately 6 weeks
Secondary outcomes:
measure: Biomarkers evaluation: analysis of apoptosis marker CK18/M30 and total soluble cytokeratin CK18/M65
timeFrame: Up to 3 years or longer if indicated
measure: Assessment of expression (IHC) and amplification status (FISH) of markers related to cell proliferation and the cell cycle in Paraffin-embedded archival tumor samples. These will include, but may not be limited to Cyclin E, Cyclin D, p21, and Ki67
timeFrame: From archival tumor blocks
measure: Functional testing of peripheral leucocytes, for example induction of cytokine synthesis
timeFrame: Approximately 6 weeks
measure: Assessment of intracellular biomarkers of apoptosis (for example activated caspase 3, annexin V, expression of MCL 1 for patients with chronic lymphocytic leucemia only
timeFrame: Approximately 6 weeks
measure: Tumor response evaluation based on RECIST 1.1 (solid tumors) or response based on the pertinent guidelines (malignant lymphoma, chronic lymphocytic leukemia) every 2 cycles
timeFrame: Up to 3 years or longer if indicated
Other outcomes:
Locations:
city: St. Louis
country: United States
state: Missouri
city: Buffalo
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Caen Cedex
country: France
city: Lyon Cedex
country: France
city: Marseille Cedex 20
country: France
city: Villejuif Cedex
country: France
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Herne
country: Germany
state: Nordrhein-Westfalen
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: