A Study of BMS-833923 With Cisplatin and Capecitabine in Inoperable, Metastatic Gastric, Gastroesophageal, or Esophageal Adenocarcinomas

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the maximum tolerated dose (MTD) of BMS-833923 administered in combination with Cisplatin and Capecitabine as first-line therapy in subjects with inoperable metastatic gastric, gastroesophageal or esophageal adenocarcinomas.

Official Title
-----------------
Phase 1b Multiple Ascending Dose Study of BMS-833923 (XL139) Administered in Combination With Cisplatin and Capecitabine as First-Line Therapy in Patients With Inoperable, Metastatic Gastric, Gastroesophageal, or Esophageal Adenocarcinomas

Conditions
-----------------
Stomach Neoplasms, Esophageal Neoplasms

Intervention / Treatment
-----------------
* Drug: BMS-833923
* Drug: Cisplatin
* Drug: Capecitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email MyCancerStudyConnect@emergingmed.com. Please visit www.BMSStudyConnect.com for more information on clinical trial participation. Inclusion Criteria: Esophageal, gastric, or gastroesophageal adenocarcinoma that has spread and cannot be treated with surgery. The diagnosis must be confirmed by a trained pathologist. Prior radiation therapy is allowed in certain circumstances - discuss with your doctor. Individuals who have had surgery may be eligible after recovering from the procedure. Individuals who have received chemotherapy for the treatment of their disease within the past 6 months are not eligible. Chemotherapy given more than 6 months ago is permitted. Individuals with spread of their cancer to the brain are permitted in certain circumstances - talk with your doctor. Exclusion Criteria: Significant heart disease. Women pregnant or breastfeeding. Women able to bear children who are unwilling or unable to use an acceptable method to avoid pregnancy. Uncontrolled medical condition or active infection Inability to swallow pills. Inability to undergo a blood draw, in which a needle is used to obtain blood from a vein in your arm. Individuals receiving another drug not approved by the Food and Drug Administration (FDA) or similar agency in another country. Prisoners or individuals currently receiving treatment for a mental or physical illness as an inpatient in a hospital. Individuals who have experienced pancreatitis, an inflammation of the pancreas, in the past, or who have had a computed axial tomography (CT) scan showing pancreatitis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 until discontinuation from study<br>Drug: Cisplatin<br>* Vial, intravenous (IV), 80 mg/m² IV, Once every 21 days, 1 day per cycle until discontinuation from study<br>* Other names: Platinol-AQ;Drug: Capecitabine<br>* Tablets, Oral, 1000 mg/m², twice a day (BID), 14 days per cycle, until discontinuation from study<br>* Other names: Xeloda;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) to establish the MTD, Dose Limiting Toxicity (DLT(s)) and safety profile of BMS-833923 administered in combination with Cisplatin and Capecitabine | MTD - maximum tolerated dose | At a minimum on days 1, 8, 15 and 35 of cycle 1, days 1 & 14 for cycle 2 and every 21 days thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety of single-agent BMS-833923, by assessing the evaluation of number, character and duration of adverse event (AE)/serious adverse event (SAE)s |  | At a minimum on days 1, 8, 15 and 35 of cycle 1, days 1 & 14 for cycle 2 and every 21 days thereafter | 
| Pharmacodynamic effects of BMS-833923 will be measured in tumor biopsy samples taken prior to and during single-agent and combination treatment by evaluation of protein or mRNA of biomarkers of Hedgehog (HH) pathway activation, such as GLI-1 | Glioma-associated oncogene (GLI) mRNA - messenger Ribonucleic acid | During cycle 1 | 
| Pharmacodynamic effects of BMS-833923 will be measured in tumor biopsy samples taken prior to and during single-agent and combination treatment by evaluation of protein or mRNA of biomarkers of Hedgehog (HH) pathway activation, such as GLI-1 | Glioma-associated oncogene (GLI) | During cycle 2 | 
| Pharmacodynamic effects of BMS-833923 will be measured in tumor biopsy samples taken prior to and during single-agent and combination treatment by evaluation of protein or mRNA of biomarkers of Hedgehog (HH) pathway activation, such as GLI-1 | Glioma-associated oncogene (GLI) | During cycle 3 | 
| The pharmacokinetic parameters that will be assessed include: Cmax (Maximum observed plasma concentration) |  | During cycles 1, 2 & 3 | 
| The pharmacokinetic parameters that will be assessed include: Tmax (Time of maximum observed plasma concentration) |  | During cycles 1, 2 & 3 | 
| The pharmacokinetic parameters that will be assessed include: AUC(TAU) (Area under the concentration-time curve in one dosing interval) |  | During cycles 1, 2 & 3 |