Clinical Study to Evaluate the Maximum Tolerated Dose of BAY1000394 When Given Together With Chemotherapy and the Effectiveness of This Combination Treatment in Shrinking a Specific Type of Lung Tumors (Small Cell Lung Cancer)

Phase 1

Terminated

Interventions: Drug: Roniciclib (BAY1000394)
Drug: Etoposide
Drug: Cisplatin
Drug: Carboplatin

Brief Summary: This is the first study where BAY1000394 is given in combination with chemotherapy: cisplatin / etoposide or carboplatin / etoposide. Patients with small cell lung cancer will be treated. Every patient will receive drug treatment, there is no placebo group. Different groups of patients will receive different dosages of BAY1000394 to determine the safety and maximum tolerated dose (MTD) of BAY1000394 in combination with chemotherapy. The dose of chemotherapy is the standard dose usually administered and will not change.

The study will also assess how the drug is metabolized by the body and changes in tumor size.

BAY1000394 will be given per mouth, twice a day for three days every week. Treatment will stop if the tumor continues to grow, if side effects occur which the patient can not tolerate or if the patients decides to exit treatment.

Recruitment & Eligibility

Inclusion Criteria

Male or female subjects aged >/=18 years
Histologically or cytologically confirmed, extensive disease SCLC
At least 1 solid tumor lesion measurable by computer tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST 1.1. Subjects with non-measurable disease according to RECIST 1.1 can be included in the Phase Ib part of the study
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
Life expectancy of at least 12 weeks
Serum sodium >/=130 mmol/L

Exclusion Criteria

Prior systemic anticancer therapy
Prior radiotherapy (local palliative radiotherapy is permitted)
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, ie Child-Pugh class B or C
Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C

Arm && Interventions

Group	Intervention	Description
Arm 1	Roniciclib (BAY1000394)	BAY1000394 will be administered in combination with chemotherapy (etoposide and cisplatin or carboplatin) for up to 6 cycles. BAY1000394 will continue beyond Cycle 6 of chemotherapy. Type of chemotherapy for each patient will be decided by the investigator case by case.
Arm 1	Cisplatin	BAY1000394 will be administered in combination with chemotherapy (etoposide and cisplatin or carboplatin) for up to 6 cycles. BAY1000394 will continue beyond Cycle 6 of chemotherapy. Type of chemotherapy for each patient will be decided by the investigator case by case.
Arm 1	Carboplatin	BAY1000394 will be administered in combination with chemotherapy (etoposide and cisplatin or carboplatin) for up to 6 cycles. BAY1000394 will continue beyond Cycle 6 of chemotherapy. Type of chemotherapy for each patient will be decided by the investigator case by case.
Arm 1	Etoposide	BAY1000394 will be administered in combination with chemotherapy (etoposide and cisplatin or carboplatin) for up to 6 cycles. BAY1000394 will continue beyond Cycle 6 of chemotherapy. Type of chemotherapy for each patient will be decided by the investigator case by case.

Primary Outcome Measures

Name	Time	Method
Area under the concentration versus time curve from zero to infinity after single (first) dose(AUC) of BAY1000394	Cycle 1, Day 8 and Cycle 2, Day 1
Safety variables will be summarized using descriptive statistics based on adverse events collection	up to 3 years
tumor response - number of subjects with best tumor response that is achieved during or within 30 days after end of therapy	up to 3 years
Maximum drug concentration in plasma after single dose administration(Cmax) of BAY1000394	Cycle 1, Day 8 and Cycle 2, Day 1
Maximum Tolerated Dose (MTD) - measured by adverse event profile at the end of Cycle 1. MTD will be the highest dose level achieved during dose escalation where non or 1 of 6 subjects experience a dose limiting toxicity as defined in the protocol	up to 3 years

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	From start of treatment of the first subject until 3 years later	time (days) from date of first treatment to death due to any cause.
Disease control rate (DCR)	From start of treatment of the first subject until 3 years later, assessed every 6 weeks	number of patients with complete response, partial response or stable disease according to RECIST
Time to progression (TTP)	From start of treatment of the first subject until 3 years later, assessed every 6 weeks	time (days) from date of first treatment to first observed radiological disease progression
Progression-free survival (PFS)	From start of treatment of the first subject until 3 years later, assessed every 6 weeks	time (days) from date of first treatment to first observed radiological disease progression or death
Duration of response (DOR)	From start of treatment of the first subject until 3 years later, assessed every 6 weeks	time (days) from date of first radiological response to the date that progressive disease is first radiologically documented or death occurs
Stable disease (SD)	From start of treatment of the first subject until 3 years later, assessed every 6 weeks	time (days) from date of first treatment to first observed radiological disease progression or death