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)

Sponsor

Bayer (Industry)

Overall Status

Terminated

CT.gov ID

NCT01573338

Collaborator

(none)

Enrollment

Locations

Arm

39.9

Actual Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Carcinoma	Drug: Roniciclib (BAY1000394) Drug: Etoposide Drug: Cisplatin Drug: Carboplatin	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Actual Study Start Date :

Feb 25, 2013

Actual Primary Completion Date :

Mar 25, 2016

Actual Study Completion Date :

Jun 23, 2016

Arms and Interventions

Arm	Intervention/Treatment
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 (BAY1000394) 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.

Arm

Intervention/Treatment

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 (BAY1000394)

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Saint Louis	Missouri	United States	63110
2	Buffalo	New York	United States	14263-0001
3	Cleveland	Ohio	United States	44195
4	Caen Cedex		France	14033
5	Marseille		France	13005
6	Villejuif Cedex		France	94805
7	Seoul		Korea, Republic of	03080
8	Seoul		Korea, Republic of	03722