Gastric/Gastroesophageal or Esophageal Adenocarcinomas - cancer of the stomach and/or esophagous
Conditions
Interventions
BMS-833923 administered with cisplatin and capecitabine as a combined therapy.
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent 2) Subjects with histologically or cytologically confirmed metastatic esophageal,gastric, or gastroesophageal adenocarcinoma. 3) Eastern Cooperative Oncology Group (ECOG) performance status 0-2 4) Estimated life expectancy of at least 3 months 5) Biopsies - Subjects in the dose escalation portion of the study will have one pre-treatment biopsy. Subjects in the dose expansion portion of the study will have one pre-treatment biopsy and two on-treatment for biomarker and predictive marker analyses. 6) No prior chemotherapy for the target disease is permitted. 7) Men and women, ages 18 and above. 8) WOCBP must have a negative serum or urine pregnancy test
Exclusion criteria
Exclusion criteria: 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 3 months after the last dose of investigational product. 2) Sexually active fertile men not using effective birth control while on study and for at least 3 months following treatment with BMS-833923. 3) Subjects with known symptomatic brain metastasis. 4) Any serious, uncontrolled medical disorder or acute infection which would impair the ability of the subject to receive protocol therapy. 5) Any gastrointestinal surgery, unresolved bowel obstruction or malabsorption syndrome that could impact the absorption of study drug. 6) Uncontrolled or significant cardiovascular disease. 7) Active or chronic infection with HIV, HepB, or HepC. 8) Positive Pregnancy Test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Toxicity will be evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, ECGs, multiple gated acquisition scan (MUGA) or echocardiograms, physical examinations, and clinical laboratory tests. Pharmacokinetic parameters including Cmax, Tmax and AUC (TAU) will be derived from plasma concentration versus time data for BMS-833923 alone on days 11-14 for any subjects undergoing tumor biopsy in the dose escalation cohort, and all subjects in the dose expansion cohort, and in combination with cisplatin and capecitabine on cycle 2 day 1 for subjects in the dose expansion cohort. | — |
Secondary
| Measure | Time frame |
|---|---|
| Trough samples for the assessment of 5-FU, the active moiety of capecitabine, will be collected on cycle 1, day 35 and cycle 2, day 14 in all subjects during dose escalation, on cycle 1, day 35, cycle 2, day 2, and cycle 2, day 14 in at least 12 subjects during dose expansion. Tumor response will be determined for all subjects by radiological responses as defined by RECIST criteria. Radiological and/or clinical tumor assessments to evaluate response and progression will be done after even cycles of therapy or more frequently if indicated. Pretreatment biopsies will serve as baseline samples for comparison with subsequent on-treatment biopsies to assess PD changes. The tumor biopsies will be used to evaluate effects of study drug treatment on mRNA and/or protein levels of Hedgehog pathway components and a marker of apoptosis. | — |
Countries
Netherlands
Outcome results
None listed