Etanercept and Gemcitabine in Patients With Advanced, Chemotherapy Naive Pancreatic Adenocarcinoma

Phase 1

Completed

Conditions: Pancreatic Neoplasms
Adenocarcinoma

Interventions: Drug: Gemcitabine
Drug: Etanercept

Registration Number: NCT00201838

Lead Sponsor: Ohio State University Comprehensive Cancer Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

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.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II	Gemcitabine	Patients with pancreatic cancer for which treatment with gemcitabine as a single agent is planned will be asked to participate in this trial as a control group.
Arm I	Gemcitabine	Patients received entanercept 25 mg subcutaneously twice weekly with gemcitabine.
Arm I	Etanercept	Patients received entanercept 25 mg subcutaneously twice weekly with gemcitabine.

Primary Outcome Measures

Name	Time	Method
Anti-tumor Effect as Measured by the Proportion of Patients Free of Disease-progression at Six Months After Treatment Initiation	up to 6 months	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Percentages were calculated by a Kaplan Meier analysis.

Secondary Outcome Measures

Name	Time	Method
Median Overall Survival Rates for Patients	up to 1 year	Median survival is defined as the time of initiation of the first dose of intervention to the date of death
Number of Patients With Response	up to 12 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Percentage of Patients With Clinical Benefit Response	Up to 12 months	A clinical benefit was defined by the improvement of at least one parameter over at least 4 weeks, without worsening of any other parameter (change in weight, ECOG performance status, Quality of life).
Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines	up to 6 months