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

NCT01188252 | Completed Phase 1

• 2 other identifiers: 144842010-019191-79
• Study Type: interventional
• Target: 112
• Locations: 3 countries
• Sites: 9

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

Conditions

Neoplasms

Keywords

Phase I; Dose escalation; Kinase inhibitor; Cyclin-dependent kinases

Outcome Measures

Primary Outcomes (3)

• Safety: Frequency of adverse events

  Up to 3 years or longer if indicated

• Maximum tolerated dose: Measured by adverse event profile

  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.

  Approximately 6 weeks

Secondary Outcomes (5)

• Biomarkers evaluation: analysis of apoptosis marker CK18/M30 and total soluble cytokeratin CK18/M65

  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

  From archival tumor blocks

• Functional testing of peripheral leucocytes, for example induction of cytokine synthesis

  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

  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

  Up to 3 years or longer if indicated

Study Arms (1)

Roniciclib

EXPERIMENTAL

Drug: Roniciclib (BAY1000394)

Interventions

Roniciclib (BAY1000394) DRUG

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.

Roniciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (9)

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Buffalo, New York, 14263-0001, United States

Location

Unknown Facility

Cleveland, Ohio, 44195, United States

Location

Unknown Facility

Caen, 14033, France

Location

Unknown Facility

Lyon, 69008, France

Location

Unknown Facility

Marseille, 13915, France

Location

Unknown Facility

Villejuif, 94805, France

Location

Unknown Facility

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Unknown Facility

Herne, North Rhine-Westphalia, 44625, Germany

Location

MeSH Terms

Conditions

Neoplasms

Interventions

roniciclib

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2010
• First Posted: August 25, 2010
• Study Start: August 1, 2010
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 9, 2017

Record last verified: 2017-01

Locations

FR (4); US (3); DE (2)