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)
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.
Small Cell Lung Carcinoma
Drug: Roniciclib (BAY 1000394)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase Ib / II Study of BAY 1000394 in Combination With Cisplatin / Etoposide or Carboplatin / Etoposide as First-line Therapy in Subjects With Extensive Disease Small Cell Lung Cancer|
- Safety variables will be summarized using descriptive statistics based on adverse events collection [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: up to 3 years ]
- Maximum drug concentration in plasma after single dose administration(Cmax) of BAY1000394 [ Time Frame: 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 [ Time Frame: Cycle 1, Day 8 and Cycle 2, Day 1 ]
- Disease control rate (DCR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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
|Study Start Date:||February 2013|
|Study Completion Date:||June 2016|
|Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
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.
Drug: Roniciclib (BAY 1000394)
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.Drug: Etoposide
100 mg/m2 will be administered IV on Days 1, 2, and 3 of each 21 day cycle.Drug: Cisplatin
75 mg/m2 will be administered IV on Day 1 of each 21 day cycle after the etoposide infusion is complete.Drug: Carboplatin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01573338
|United States, Missouri|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Buffalo, New York, United States, 14263-0001|
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|Caen Cedex, France, 14033|
|Lyon Cedex, France, 69008|
|Marseille, France, 13005|
|Villejuif Cedex, France, 94805|
|Korea, Republic of|
|Seoul, Korea, Republic of, 03080|
|Seoul, Korea, Republic of, 120-752|
|Study Director:||Bayer Study Director||Bayer|