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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01188252
• Date of registration: 30/07/2010
• Prospective Registration: Yes
• Primary sponsor: Bayer
• Public title: 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
• Scientific 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
• Date of first enrolment: August 2010
• Target sample size: 112
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01188252
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

France, Germany, United States

Contacts

• Name: Bayer Study Director
• Affiliation: Bayer

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Neoplasms

Intervention(s)

Drug: Roniciclib (BAY1000394)

Primary Outcome(s)

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]

Safety: Frequency of adverse events [Time Frame: Up to 3 years or longer if indicated]

Secondary Outcome(s)

Functional testing of peripheral leucocytes, for example induction of cytokine synthesis [Time Frame: Approximately 6 weeks]

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]

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]

Biomarkers evaluation: analysis of apoptosis marker CK18/M30 and total soluble cytokeratin CK18/M65 [Time Frame: Up to 3 years or longer if indicated]

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]

Secondary ID(s)

2010-019191-79

14484

Source(s) of Monetary Support

Please refer to primary and secondary sponsors