ADH-1, Gemcitabine Hydrochloride and Cisplatin in Treating Patients With Metastatic Pancreatic or Biliary Tract Cancer That Cannot Be Removed By Surgery
Conditions
Acinar Cell Adenocarcinoma of the Pancreas - Adenocarcinoma of the Gallbladder - Adult Primary Cholangiocellular Carcinoma - Advanced Adult Primary Liver Cancer - Cholangiocarcinoma of the Gallbladder - Duct Cell Adenocarcinoma of the Pancreas - Localized Unresectable Adult Primary Liver Cancer - Periampullary Adenocarcinoma - Recurrent Adult Primary Liver Cancer - Recurrent Gallbladder Cancer - Recurrent Pancreatic Cancer - Stage II Gallbladder Cancer - Stage III Pancreatic Cancer - Stage IIIA Gallbladder Cancer - Stage IIIB Gallbladder Cancer - Stage IV Pancreatic Cancer - Stage IVA Gallbladder Cancer - Stage IVB Gallbladder Cancer
Conditions: official terms
Adenocarcinoma - Carcinoma, Acinar Cell - Cholangiocarcinoma - Gallbladder Neoplasms - Liver Neoplasms - Pancreatic Neoplasms
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: ADH-1 Type: Drug
Name: cisplatin Type: Drug
Name: gemcitabine hydrochloride Type: Drug
Name: laboratory biomarker analysis Type: Other
Overall Status
Recruiting
Summary
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 metastatic pancreatic or biliary tract cancer that 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 or by stopping them from dividing. Giving ADH-1 together with gemcitabine hydrochloride and cisplatin may kill more tumor cells.
Detailed Description
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:

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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 19 Years
Gender: Both
Criteria: Inclusion Criteria:

- Patients must have adenocarcinoma of the pancreas or biliary tree (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder or ampulla of Vater) that is locally advanced, but non-resectable, metastatic or residual disease after attempted surgical resection

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or better

- Absolute neutrophil count (ANC) of 2000 per mcL or higher

- Platelet count of 100,000 per mcL or higher

- Patients must have a serum creatinine that is at or below the upper limits of the institutional normal range OR a creatinine clearance of 60 mL per min or higher corrected for body surface area (BSA)

- The total bilirubin must be at or below 2.0 mg/dL in the absence of biliary obstruction; if the patient has biliary obstruction, biliary decompression will be required; either endoscopic placement of a biliary stent or percutaneous transhepatic drainage is acceptable; once biliary drainage has been established, institution of protocol therapy may proceed when the total bilirubin falls to 3.0 mg/dL or lower

- Patients need not have measurable disease for this study

- The patient must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts

- Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment

- Women of child-bearing potential must have a negative pregnancy test within 7 days of initiating study; (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)

Exclusion Criteria:

- Patients may not have received prior chemotherapy for metastatic adenocarcinoma of the pancreas or biliary tract; prior adjuvant chemotherapy is acceptable provided that 6 months or longer has elapsed since completion of the prior therapy

- History of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy

- Uncontrolled inter-current illness including, but not limited to ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, or serious, uncontrolled cardiac arrhythmia, that might jeopardize the ability of the patient to receive the chemotherapy program outlined in this protocol with reasonable safety

- Pregnant and nursing women are excluded from this study because the chemotherapy agents have the potential for teratogenic or abortifacient effects

- Patients with prior malignancy will be excluded except for adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinomas, or other cancers from which the patient has been disease-free for at least 5 years
Location
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States
Status: Recruiting
Contact: Jean L. Grem - 800-999-5465 - jgrem@unmc.edu
Start Date
April 2013
Sponsors
University of Nebraska
Source
University of Nebraska
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page