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

Sponsor:	Bristol-Myers Squibb
Collaborator:	Exelixis
Information provided by (Responsible Party):	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00909402

Purpose

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	Intervention	Phase
Stomach Neoplasms Esophageal Neoplasms	Drug: BMS-833923 Drug: Cisplatin Drug: Capecitabine	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Stomach Cancer

Drug Information available for: Cisplatin Capecitabine

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

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 [ Time Frame: At a minimum on days 1, 8, 15 and 35 of cycle 1, days 1 & 14 for cycle 2 and every 21 days thereafter ] [ Designated as safety issue: Yes ]
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 [ Time Frame: At a minimum on days 1, 8, 15 and 35 of cycle 1, days 1 & 14 for cycle 2 and every 21 days thereafter ] [ Designated as safety issue: Yes ]
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 [ Time Frame: During cycle 1 ] [ Designated as safety issue: No ]
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 [ Time Frame: During cycle 2 ] [ Designated as safety issue: No ]
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 [ Time Frame: During cycle 3 ] [ Designated as safety issue: No ]
Glioma-associated oncogene (GLI)
The pharmacokinetic parameters that will be assessed include: Cmax (Maximum observed plasma concentration) [ Time Frame: During cycles 1, 2 & 3 ] [ Designated as safety issue: No ]
The pharmacokinetic parameters that will be assessed include: Tmax (Time of maximum observed plasma concentration) [ Time Frame: During cycles 1, 2 & 3 ] [ Designated as safety issue: No ]
The pharmacokinetic parameters that will be assessed include: AUC(TAU) (Area under the concentration-time curve in one dosing interval) [ Time Frame: During cycles 1, 2 & 3 ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	November 2009
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: Platinol-AQ Drug: Capecitabine Tablets, Oral, 1000 mg/m², twice a day (BID), 14 days per cycle, until discontinuation from study Other Name: Xeloda

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00909402

Contacts

Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:		Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations

United States, California
City Of Hope National Medical Center	Recruiting
Duarte, California, United States, 91010
Contact: Stephen Shibata, Site 006
Usc/Norris Comprehensive Cancer Center	Recruiting
Los Angeles, California, United States, 90033
Contact: Anthony El-Khoueiry, Site 001 323-865-3967
United States, Texas
The University Of Texas Md Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Jaffer A. Ajani, Site 007
Canada, Ontario
Local Institution	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Site 005
France
Local Institution	Recruiting
Villejuif, France, 94805
Contact: Site 008
Korea, Republic of
Local Institution	Not yet recruiting
Seoul, Korea, Republic of, 136-705
Contact: Site 004
Netherlands
Local Institution	Recruiting
Amsterdam, Netherlands, 1105 AZ
Contact: Site 009

Sponsors and Collaborators

Bristol-Myers Squibb

Exelixis

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00909402 History of Changes
Other Study ID Numbers:	CA194-004, 2010-018743-33
Study First Received:	May 22, 2009
Last Updated:	February 2, 2012
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada; Korea: Food and Drug Administration

Additional relevant MeSH terms:

Adenocarcinoma
Neoplasms
Esophageal Diseases
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms

Stomach Diseases
Capecitabine
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on February 09, 2012