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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase I/II Study of Etanercept and Gemcitabine in Patients With Advanced Stage and Chemotherapy Naive Pancreatic Adenocarcinoma

Conditions
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Pancreatic Neoplasms, Adenocarcinoma

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients received entanercept 25 mg subcutaneously twice weekly with gemcitabine. | Drug: Gemcitabine<br>* The starting dose will be 1000mg/m2 IV, weekly x 7 with a one week rest followed by weekly x 3 with one week rest for the remainder of treatment.<br>* Other names: Gemzar®;Drug: Etanercept<br>* Etanercept will be self administered subcutaneously by patients with injections 11 prepared by the investigational pharmacy, beginning 7 days prior to the first dose of gemcitabine and continued twice weekly for the duration of the study.<br>* Other names: Enbrel;|
| Active Comparator: Arm II<br>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. | Drug: Gemcitabine<br>* The starting dose will be 1000mg/m2 IV, weekly x 7 with a one week rest followed by weekly x 3 with one week rest for the remainder of treatment.<br>* Other names: Gemzar®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor Effect as Measured by the Proportion of Patients Free of Disease-progression at Six Months After Treatment Initiation | 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. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Response | 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. | up to 12 months | 
| Percentage of Patients With Clinical Benefit Response | 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). | Up to 12 months | 
| Median Overall Survival Rates for Patients | Median survival is defined as the time of initiation of the first dose of intervention to the date of death | up to 1 year | 
| Serial Levels of TNF (Tumor Necrosis Factor) and Other Inflammatory Cytokines |  | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy Naive, Advanced Stage