Etanercept and Gemcitabine in Patients With Advanced, Chemotherapy Naive Pancreatic Adenocarcinoma
The aims of this protocol are:
- To study the safety and tolerability of the combination of etanercept and gemcitabine in patients with advanced pancreatic cancer:
- To estimate the anti-tumor effect as measured by the proportion of patients free of disease-progression at six months after treatment initiation.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Etanercept and Gemcitabine in Patients With Advanced Stage and Chemotherapy Naive Pancreatic Adenocarcinoma|
- anti-tumor effect as measured by the proportion of patients free of disease-progression at six months after treatment initiation [ Time Frame: 2001-2010 ] [ Designated as safety issue: Yes ]
- Clinical Benefit Response as defined by pain intensity and analgesic use, [ Time Frame: 2001-2010 ] [ Designated as safety issue: No ]
- change in weight, ECOG performance status, and quality of life [ Time Frame: 2001-2010 ] [ Designated as safety issue: Yes ]
- Median survival and survival rates at 6 and 12 months [ Time Frame: 2001-2010 ] [ Designated as safety issue: No ]
- serial levels of TNF and other inflammatory cytokines [ Time Frame: 2001-2010 ] [ Designated as safety issue: No ]
|Study Start Date:||July 2001|
|Study Completion Date:||May 2007|
|Primary Completion Date:||October 2006 (Final data collection date for primary outcome measure)|
Rationale: The standard treatment for pancreatic cancer is gemcitabine. This study combines gemcitabine with etanercept, a drug that binds with tumor necrosis factor (TNF) molecules and blocks their activity through inhibiting their interaction with cell surface TNF receptors. TNF is the name for a protein in the body that often helps fight foreign substances. However, research suggests that pancreatic tumors develop resistance to TNF and then use it to support cancer growth. Combining etanercept, a TNF inhibitor, with gemcitabine is a novel approach to advanced pancreatic cancer. Because etanercept has not been tested in combination with gemcitabine, a Phase I study will be conducted first to identify the safest dosage of etanercept, and then a Phase II study will evaluate the efficacy of this combination.
Purpose: This study is evaluating the safety of etanercept and gemcitabine for advanced pancreatic cancer in Phase I, and the efficacy of etanercept and gemcitabine for this condition in Phase II. TNF and other inflammatory markers will also be measured in the study.
Treatment: Patients in this study will receive gemcitabine and etanercept. Gemcitabine will be administered through an intravenous infusion weekly for seven weeks followed by one week of rest. Additional treatments with gemcitabine will be given for three weeks followed by one week of rest. Patients will administer etanercept to themselves through a small injection underneath the skin twice each week. Six patients will initially be enrolled in Phase I. If severe side effects appear in at least two patients in Phase I, then additional patients will be enrolled and treated with lower dosages of gemcitabine. When the treatments do not produce unacceptable side effects, the Phase I portion of the study will end and Phase II will begin enrolling patients. Patients in the Phase II portion of the study will also receive gemcitabine and etanercept at the safest dosages identified in Phase I. Several tests and exams will be given throughout both portions of the study to closely monitor patients. Treatments will be discontinued due to disease growth or unacceptable side effects.
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Miguel Villalona||Ohio State University|