A Study of BMS-833923 With Carboplatin and Etoposide Followed by BMS-833923 Alone in Subjects With Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the maximum tolerated dose (MTD) of BMS-833923 administered in combination with carboplatin and etoposide followed by BMS-833923 alone in subjects with extensive-stage Small Cell Lung Cancer (SCLC).

Official Title
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A Phase 1b Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-833923 (XL139) in Combination With Carboplatin and Etoposide Followed by BMS-833923 Alone in Subjects With Extensive-Stage Small Cell Lung Cancer

Conditions
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Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: BMS-833923
* Drug: Carboplatin
* Drug: Etoposide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed small cell lung cancer, without prior chemotherapy treatment Men and Women at least 18 years old Eastern Cooperative Oncology Group (ECOG) status 0-2 Exclusion Criteria: Significant cardiovascular disease Prior treatment of small cell lung cancer is not permitted, except for palliative radiation to a limited field excluding the chest (e.g. for painful metastasis). Symptomatic brain metastases Women pregnant or breastfeeding Women of childbearing potential (WOCBP) unwilling/unable to use acceptable method to avoid pregnancy Uncontrolled medical disorder or active infection Concurrent therapy with any other investigational product

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Subjects<br> | Drug: BMS-833923<br>* Capsule, Oral, starting dose 30 mg, once daily, continuous<br>Drug: Carboplatin<br>* Vial, Intravenous (IV), dose to yield 5 mg/mL - min, once every 21 days, 1 day per cycle up to 4 cycles<br>* Other names: Paraplatin®;Drug: Etoposide<br>* Vial, Intravenous (IV), 100 mg/m²/dose, days 1, 2, & 3 of each 21 day cycle, 3 days per cycle for up to 4 cycles<br>* Other names: VePesid®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use NCI CTCAE to establish the MTD, DLT(s) and safety profile of BMS-833923 administered alone and in combination with carboplatin and etoposide | NCI - National Cancer Institute CTCAE - Common Terminology Criteria for Adverse Events MTD - Maximum tolerated dose DLT - Dose limiting toxicity | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of BMS-833923 alone and in combination with carboplatin and etoposide: Maximum observed plasma concentration (Cmax) |  | Day 1 and 15 of first three 21-day cycles | 
| Pharmacokinetic parameters of BMS-833923 alone and in combination with carboplatin and etoposide: Time of maximum observed plasma concentration (Tmax) |  | Day 1 and 15 of first three 21-day cycles | 
| Pharmacokinetic parameters of BMS-833923 alone and in combination with carboplatin and etoposide: Area under the concentration-time curve in one dosing interval AUC(TAU) |  | Day 1 and 15 of first three 21-day cycles | 
| Tumor assessments by computed tomography (CT) [as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1] |  | Every 6 weeks until disease progression | 
| Pharmacodynamic effect (change from baseline) of BMS-833923 on Hedgehog pathway activation as measured by Glioma-associated oncogene -1 (GLI-1) expression |  | At baseline and after 1 week |