This phase I trial studies the side effects and best dose of ADH-1 when given together with gemcitabine hydrochloride and cisplatin in treating patients with pancreatic or biliary tract cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or spread to other parts of the body (metastatic) and cannot be removed by surgery. ADH-1 may stop the growth of cancer cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ADH-1 together with gemcitabine hydrochloride and cisplatin may kill more tumor cells.
PRIMARY OBJECTIVES: I. To evaluate the toxicities and determine the recommended dose of ADH-1 given twice weekly for 3 weeks in combination with cisplatin and fixed-dose rate gemcitabine (gemcitabine hydrochloride) given on weeks 1 and 2 of the 3 week schedule for 3 cycles in patients with locally advanced or metastatic pancreatic or biliary tract adenocarcinomas. SECONDARY OBJECTIVES: I. To evaluate changes in the levels of intercellular adhesion molecule 1 (ICAM-1), E-selectin, vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor (VEGFR) and basic fibroblast growth factor (B-FGF) during therapy with ADH-1, cisplatin and gemcitabine. II. Radiographic assessment of disease status after 3 cycles of chemotherapy with ADH-1, cisplatin and gemcitabine. III. To evaluate progression-free and overall survival of patients with locally advanced or metastatic pancreatic or biliary tract adenocarcinomas treated with ADH-1 given with cisplatin and fixed dose rate gemcitabine for 3 cycles. Patients with stable or responsive disease after 3 cycles will continue on maintenance cisplatin and fixed dose rate gemcitabine. OUTLINE: This is a dose-escalation study of ADH-1. Patients receive ADH-1 intravenously (IV) over 20-80 minutes on days 1, 4, 8, 11, 15, and 18, cisplatin IV and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease may receive maintenance therapy with cisplatin and gemcitabine hydrochloride. After completion of study treatment, patients are followed up every 3 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
University of Nebraska Medical Center
Omaha, Nebraska, United States
Recommended dose of ADH-1, defined as the highest dose tested which results in dose-limiting toxicities in no more than 1 of 6 evaluable patients based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
The incidence rates of adverse events will be described by dose level. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described.
Time frame: 21 days
Changes in the levels of ICAM-1, E-selectin, VEGF, soluble VEGFR and B-FGF
Summarized using descriptive statistics
Time frame: After all patients complete cycle 1, about 2 years after initial patient enrolled
Progression-free survival
Plotted following the method of Kaplan and Meier.
Time frame: From the first date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 2 years
Survival
Plotted following the method of Kaplan and Meier.
Time frame: From the first date of therapy until the date of death from any cause, assessed up to 2 years
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