Clinical Study to Evaluate Safety and Maximum Tolerated Dose of BAY1000394 Given in a 4 Week on / 2 Week Off Schedule in Subjects With Advanced Malignancies

An Open-label, Phase I, Dose-escalation Study to Characterize the Safety, Tolerability, Pharmacokinetics, and Maximum Tolerated Dose of BAY1000394 Given in a 4 Week on / 2 Week Off Schedule in Subjects With Advanced Malignancies

Clinical study to determine safety, tolerability, and maximum tolerated dose of BAY1000394 given in 4 week on / 2 week off schedule to patients with advanced solid tumors

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: BAY1000394

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
  • Missouri
    • St. Louis, Missouri, United States, 63110
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• 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
• Estimated creatinine clearance 60 mL/min according to Modification of Diet in Renal Disease Study Group (MDRD) formula(2)
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the first dose of study drug
• Subjects with a history of hypertension should be on a stable anti-hypertensive treatment for more than 7 days prior to the first dose of study drug
• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study-specific procedures.

Exclusion Criteria:

• Any patient with potentially curable disease will be explicity excluded from enrollment into the study
• Known hypersensitivity to the study drug (active investigational medicinal product or excipients of the preparations) or any agent given in association with this study
• History of cardiac disease: congestive heart failure > NYHA Class II, unstable angina (anginal symptoms at rest), new-onset angina (within the past 3 months prior to study entry), myocardial infarction within the past 3 months prior to study entry, or cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
• 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
• 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
• Previous or coexisting cancer that is distinct in primary site or histology from the cancer evaluated in this study EXCEPT cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors [Ta and Tis], or any cancer curatively treated >3 years prior to study entry
• Anticancer chemotherapy or immunotherapy within 4 weeks of study entry. Mitomycin C or nitrosoureas should not be given within 6 weeks of study entry. Anticancer therapy is defined as any agent or combination of agents with clinically proven anti tumor activity administered by any route with the purpose of affecting the malignancy, either directly or indirectly, including palliative and therapeutic endpoints. Accepted exceptions are bisphosphonates, Luteinizing hormone-releasing hormone (LHRH) agonists for prostate cancer, and mitotane for adrenal carcinoma.
• Radiotherapy to target lesions within 3 weeks prior to the first dose of study drug. Palliative radiotherapy will be allowed as described in Section 6.9 of this protocol. Radiotherapy to the target lesions during study will be regarded as progressive disease
• Use of biological response modifiers, such as granulocyte-colony stimulating factor (G-CSF), within 3 weeks prior to the first dose of study drug. Granulocyte-colony stimulating factor (G-CSF) and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however, they may not be substituted for a required dose reduction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: BAY1000394; BAY1000394 will be administered orally twice a day (bid) in a 4 week on / 2 week off schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose: Measured by adverse event profile	Up to 3 years or longer if indicated
Number of subjects with Adverse Events as a measure safety	Up to 3 years or longer if indicated

Secondary Outcome Measures

Outcome Measure	Time Frame
Tumor Response evaluation measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	Up to 3 years or longer if indicated
Biomarkers evaluation measured by Enzyme-linked immunosorbent assay (ELISA)	Up to 3 years or longer if indicated
Peak Plasma Concentration (Cmax) of BAY1000394	Approximately 18 months
Pharmacokinetics parameters will be measured using Peak Plasma Time (tmax) of BAY1000394	Approximately 18 months
Area under the plasma concentration versus time curve from 0 to tn (AUC(0 tn)) of BAY1000394	Approximately 18 months
Area under the plasma concentration versus time curve (AUC) of BAY1000394	Approximately 18 months
Half-life of BAY1000394	Approximately 18 months

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: January 10, 2011
• First Submitted That Met QC Criteria: April 13, 2011
• First Posted (Estimate): April 14, 2011

Study Record Updates

• Last Update Posted (Estimate): May 3, 2013
• Last Update Submitted That Met QC Criteria: May 1, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Phase I, dose escalation, kinase inhibitor, cyclin-dependent kinase inhibitor, target therapy, small molecule
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 14856; 2010-019191-79 (EudraCT Number)