Small Cell Lung Carcinoma
Conditions
Keywords
Cyclin dependent kinases, Drug therapy, combination, Small cell lung carcinoma, Etoposide, Cisplatin, 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.
Interventions
oral administration twice daily in a 3 days on/ 4 days off schedule. Starting dose will be 2.5 mg bid and dose will be escalated or de-escalated depending on dose limiting toxicity.
DRUGEtoposide
100 mg/m2 will be administered IV on Days 1, 2, and 3 of each 21 day cycle.
DRUGCisplatin
75 mg/m2 will be administered IV on Day 1 of each 21 day cycle after the etoposide infusion is complete.
DRUGCarboplatin
Carboplatin will be administered IV on Day 1 of each 21 day cycle. The dose of carboplatin will be determined for each cycle using the Calvert's formula, to yield an AUC of 5 (mg/mL) • min.
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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 |
| Maximum drug concentration in plasma after single dose administration(Cmax) of BAY1000394 | Cycle 1, Day 8 and Cycle 2, Day 1 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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. |
| 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 |
Countries
France, South Korea, United States
Outcome results
None listed