This trial has been completed.

Condition neoplasms
Treatment roniciclib (bay1000394)
Phase phase 1
Sponsor Bayer
Start date August 2010
End date June 2016
Trial size 112 participants
Trial identifier NCT01188252, 14484, 2010-019191-79


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

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
roniciclib (bay1000394)
Oral administration twice daily in a 3 days on / 4 days off schedule. Starting dose will be 0.3 mg corresponding to approximately 0.005 mg/kg and dose will be escalated dependent on any dose limiting toxicities.

Primary Outcomes

Safety: Frequency of adverse events
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: Plasma concentrations of BAY1000394 will be measured. The following parameters will be calculated: Cmax, tmax, AUC(0-tn), AUC, and half-life.
time frame: Approximately 6 weeks

Secondary Outcomes

Biomarkers evaluation: analysis of apoptosis marker CK18/M30 and total soluble cytokeratin CK18/M65
time frame: Up to 3 years or longer if indicated
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
time frame: From archival tumor blocks
Functional testing of peripheral leucocytes, for example induction of cytokine synthesis
time frame: Approximately 6 weeks
Assessment of intracellular biomarkers of apoptosis (for example activated caspase 3, annexin V, expression of MCL 1 for patients with chronic lymphocytic leucemia only
time frame: Approximately 6 weeks
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
time frame: Up to 3 years or longer if indicated

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in January 2017.
Information provided to ClinicalTrials.gov by Bayer.