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

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Completed

CT.gov ID

NCT00909402

Collaborator

Exelixis (Industry)

Enrollment

Locations

Arm

Duration (Months)

6.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Stomach Neoplasms Esophageal Neoplasms	Drug: BMS-833923 Drug: Cisplatin Drug: Capecitabine	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All Subjects	Drug: BMS-833923 Capsule, Oral, Starting dose 30 mg, Once daily, continuous until discontinuation from study Drug: Cisplatin Vial, intravenous (IV), 80 mg/m² IV, Once every 21 days, 1 day per cycle until discontinuation from study Other Names: Platinol-AQ Drug: Capecitabine Tablets, Oral, 1000 mg/m², twice a day (BID), 14 days per cycle, until discontinuation from study Other Names: Xeloda

Arm

Intervention/Treatment

Experimental: All Subjects

Drug: BMS-833923

Capsule, Oral, Starting dose 30 mg, Once daily, continuous until discontinuation from study

Drug: Cisplatin

Vial, intravenous (IV), 80 mg/m² IV, Once every 21 days, 1 day per cycle until discontinuation from study

Other Names:

Platinol-AQ

Drug: Capecitabine

Tablets, Oral, 1000 mg/m², twice a day (BID), 14 days per cycle, until discontinuation from study

Other Names:

Xeloda

Outcome Measures

Primary Outcome Measures

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 [At a minimum on days 1, 8, 15 and 35 of cycle 1, days 1 & 14 for cycle 2 and every 21 days thereafter]
MTD - maximum tolerated dose

Secondary Outcome Measures

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 [During cycle 1]
Glioma-associated oncogene (GLI) mRNA - messenger Ribonucleic acid
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 [During cycle 2]
Glioma-associated oncogene (GLI)
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 [During cycle 3]
Glioma-associated oncogene (GLI)
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City Of Hope National Medical Center	Duarte	California	United States	91010-3012
2	Usc/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
3	The University Of Texas Md Anderson Cancer Center	Houston	Texas	United States	77030-4009
4	Local Institution	Toronto	Ontario	Canada	M5G 2M9
5	Local Institution	Villejuif		France	94805
6	Local Institution	Amsterdam		Netherlands	1105 AZ