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

This study has been completed.
Sponsor:
Collaborator:
Exelixis
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00909402
First received: May 22, 2009
Last updated: June 20, 2013
Last verified: June 2013
  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 1

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:


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 ]

Enrollment: 39
Study Start Date: November 2009
Study Completion Date: November 2012
Primary Completion Date: November 2012 (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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
City Of Hope National Medical Center
Duarte, California, United States, 91010-3012
Usc/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, Texas
The University Of Texas Md Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Canada, Ontario
Local Institution
Toronto, Ontario, Canada, M5G 2M9
France
Local Institution
Villejuif, France, 94805
Netherlands
Local Institution
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
Bristol-Myers Squibb
Exelixis
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
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: June 20, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Korea: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Capecitabine
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014