Study Completed

Neoplasms

Bayer Identifier:

14484

ClinicalTrials.gov Identifier:

NCT01188252

EudraCT Number:

2010-019191-79

EU CT Number:

Not Available

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

Trial purpose

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

Key Participants Requirements

Sex

Both

Age

18 - N/A

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

Trial summary

Enrollment Goal

112

Trial Dates

August 2010 - December 2016

Phase

Phase 1

Could I Receive a placebo

Products

Roniciclib (BAY1000394)

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed		VILLEJUIF CEDEX, 94805, France
Completed		Marseille Cedex 20, 13915, France
Completed		Herne, 44625, Germany
Completed		LYON CEDEX, 69008, France
Completed		CAEN CEDEX, 14033, France
Completed		St. Louis, 63110, United States
Completed		Heidelberg, 69120, Germany
Terminated		Cleveland, 44195, United States
Completed		Buffalo, 14263-0001, United States

Primary Outcome

Safety: Frequency of adverse events
Time Frame:
Up to 3 years or longer if indicated
Safety Issue:
Yes
Maximum tolerated dose: Measured by adverse event profile
Time Frame:
Up to 3 years or longer if indicated
Safety Issue:
Yes
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 Issue:
Yes

Secondary Outcome

Biomarkers evaluation: analysis of apoptosis marker CK18/M30 and total soluble cytokeratin CK18/M65
Time Frame:
Up to 3 years or longer if indicated
Safety Issue:
Yes
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
Safety Issue:
Yes
Functional testing of peripheral leucocytes, for example induction of cytokine synthesis
Time Frame:
Approximately 6 weeks
Safety Issue:
Yes
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
Safety Issue:
Yes
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
Safety Issue:
Yes

Trial design

An open-label, Phase I, dose-escalation study to characterize the safety, tolerability, pharmacokinetics, and maximum tolerated dose of BAY 1000394 given in a 3 days on / 4 days off schedule in subjects with advanced malignancies

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

N/A

Blinding

Open Label

Assignment

Single Group Assignment

Trial Arms

Additional Information

Click here and search for drug information provided by the FDA.Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.Click here to find information about studies related to Bayer AG products conducted in Europe.Click here to find results for studies related to Bayer Healthcare products.