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

November 28, 2017 updated by: Ohio State University Comprehensive Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
Patients received entanercept 25 mg subcutaneously twice weekly with gemcitabine.
Drug: Gemcitabine
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.
Other Names:
  • Gemzar®
Drug: Etanercept
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.
Other Names:
  • Enbrel
Active Comparator: Arm II
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
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.
Other Names:
  • Gemzar®

What is the study measuring?

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
Time Frame: 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.
up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Response
Time Frame: 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.
up to 12 months
Percentage of Patients With Clinical Benefit Response
Time Frame: 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).
Up to 12 months
Median Overall Survival Rates for Patients
Time Frame: up to 1 year
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
Time Frame: up to 6 months
up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ohio State University Comprehensive Cancer Center

Collaborators

Immunex Corporation

Investigators

  • Principal Investigator: Miguel Villalona, Ohio State University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2001

Primary Completion (Actual)

October 1, 2006

Study Completion (Actual)

May 1, 2007

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 20, 2005

Study Record Updates

Last Update Posted (Actual)

November 30, 2017

Last Update Submitted That Met QC Criteria

November 28, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OSU-0041

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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