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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: BAY1000394


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers evaluation measured by Enzyme-linked immunosorbent assay (ELISA) |  | Up to 3 years or longer if indicated | 
| Tumor Response evaluation measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, dose escalation, kinase inhibitor, cyclin-dependent kinase inhibitor, target therapy, small molecule