Clinical trial NCT00201838: Etanercept and Gemcitabine in Patients With Advanced, Chemotherapy Naive Pancreatic Adenocarcinoma
Official title: A Phase I/II Study of Etanercept and Gemcitabine in Patients With Advanced Stage and Chemotherapy Naive Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Neoplasms
Adenocarcinoma
Keywords: Advanced Stage
Chemotherapy Naive
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Immunex Corporation
First posted: 2005-09-20
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aims of this protocol are:

1. To study the safety and tolerability of the combination of etanercept and gemcitabine in patients with advanced pancreatic cancer:
2. To estimate the anti-tumor effect as measured by the proportion of patients free of disease-progression at six months after treatment initiation.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Must have pathological diagnosis recurring or metastatic Pancreatic Adenocarcinoma
* No prior chemotherapy, immunology treatments or hormonal treatments
* Measurable disease
* Must be \>18 years old
* ONLY CONTROL ARM IS OPEN TO ACCRUAL

Inclusion Criteria:

* Pregnant and nursing mothers.
* Psychiatric disorders that would interfere with consent ability.
* Patients with known brain or leptomeningeal disease.
* Patients with history of myocardial infarction with in six previous months.
* Any concurrent illness that would constitute a hazard to participation in study.
* Known sensitivity to gemcitabine or etanercept.
* Prior treatment with etanercept.

Primary outcomes:
measure: Anti-tumor Effect as Measured by the Proportion of Patients Free of Disease-progression at Six Months After Treatment Initiation
timeFrame: up to 6 months
Secondary outcomes:
measure: Number of Patients With Response
timeFrame: up to 12 months
measure: Percentage of Patients With Clinical Benefit Response
timeFrame: Up to 12 months
measure: Median Overall Survival Rates for Patients
timeFrame: up to 1 year
measure: Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines
timeFrame: up to 6 months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Miguel Villalona
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu C, Fernandez SA, Criswell T, Chidiac TA, Guttridge D, Villalona-Calero M, Bekaii-Saab TS. Disrupting cytokine signaling in pancreatic cancer: a phase I/II study of etanercept in combination with gemcitabine in patients with advanced disease. Pancreas. 2013 Jul;42(5):813-8. doi: 10.1097/MPA.0b013e318279b87f.