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: Gastric/Gastroesophageal or Esophageal Adenocarcinomas - cancer of the stomach and/or esophagous
10017991

Registration Number: NL-OMON34104

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 5

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Toxicity will be evaluated according to the NCI Common Terminology Criteria for<br /><br>Adverse Events (CTCAE) v3.0. Safety assessments will be based on medical review<br /><br>of adverse event reports and the results of vital sign measurements, ECGs,<br /><br>multiple gated acquisition scan (MUGA) or<br /><br>echocardiograms, physical examinations, and clinical laboratory tests.<br /><br>Pharmacokinetic parameters including Cmax, Tmax and AUC (TAU) will be derived<br /><br>from plasma concentration versus time data for BMS-833923 alone on days 11-14<br /><br>for any subjects undergoing tumor biopsy in the dose escalation cohort, and all<br /><br>subjects in the dose expansion cohort, and in combination with cisplatin and<br /><br>capecitabine on cycle 2 day 1 for subjects in the dose expansion cohort.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Trough samples for the assessment of 5-FU, the active moiety of capecitabine,<br /><br>will be collected on cycle 1, day 35 and cycle 2, day 14 in all subjects during<br /><br>dose escalation, on cycle 1, day 35, cycle 2, day 2, and cycle 2, day 14 in at<br /><br>least 12 subjects during dose expansion. Tumor response will be determined for<br /><br>all subjects by radiological responses as defined by RECIST criteria.<br /><br>Radiological and/or clinical tumor assessments to evaluate response and<br /><br>progression will be done after even cycles of therapy or more frequently if<br /><br>indicated.<br /><br><br /><br>Pretreatment biopsies will serve as baseline samples for comparison with<br /><br>subsequent on-treatment biopsies to assess PD changes. The tumor biopsies will<br /><br>be used to evaluate effects of study drug treatment on mRNA and/or protein<br /><br>levels of Hedgehog pathway components and a marker of apoptosis. </p><br>