Safety Study on the Transfer of the CD40 Ligand Gene (AdcuCD40L) to Patients With Esophageal Carcinoma

May 2, 2016 updated by: Weill Medical College of Cornell University

Phase I, Initial Safety/Toxicity Study on the Transfer of Adenovirus With the CD40 Ligand Gene (AdCUCD40L) to Patients With Stage III or IV Esophageal Carcinoma

This a pilot clinical study focused on enhancing the patient's anti-tumor immune response in individuals with esophageal cancer by altering the genetic repertoire of the tumors to express CD40L, an activator of dendritic cells. This will be accomplished by endoscopic administration to the tumors of AdcuCD40L, an adenovirus gene transfer vector expressing the coding sequence of the human CD40L cDNA. This study is designed to assess the hypothesis that it is safe to administer the AdcuCD40L vector to individuals with esophageal cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Esophageal cancer is a deadly disease, with only slow advances in therapy over several decades, despite a rapid increase in incidence. Esophageal cancer is estimated to be the seventh most common malignancy worldwide, with incidence rates reaching epidemic proportions in select regions in Asia and Africa. In the United States, it is estimated that 12,300 new cases were diagnosed in 2000, however, the incidence of adenocarcinoma of the esophagus is currently rising faster than that of any other human malignant tumor in this country. Despite advances in surgical technique, chemotherapy, radiotherapy and early detection, only 12% of patients diagnosed with esophageal cancer will survive more than five years, a cure rate more dismal than that seen with cancers of the breast, prostate, colon, and even lung. Survival following treatment for esophageal cancer is stage dependent. This study is directed towards augmenting host anti-tumor immunity by using gene transfer to activate dendritic cells (DC; cells of our immune system that play a central role in initiating immune responses) in tumors of patients with esophageal cancer. Based on extensive pre-clinical data, two proposed clinical trial protocols will evaluate the concept that transient modification of the genetic repertoire of esophageal tumors to express CD40 Ligand (CD40L; a potent activator of DC) will induce the accumulation of activated DC within the tumor, and the in vivo interaction of DC with the tumor cells/tumor antigens will induce tumor-specific immunity. To assess this concept, an adenovirus (Ad) vector (AdcuCD40L) will be used to transfer and transiently express the human CD40L cDNA in esophageal carcinoma by direct injection into the tumor. Phase I represents a dose escalation study to determine the maximum tolerated dose of the vector and will include 12 individuals with unresectable, stage III or IV esophageal cancer. Phase II is a randomized, double-blinded assessment of biologic efficacy and will include 24 individuals with resectable, stage I-III disease who will be undergoing potentially curative resection. Together, both protocols are designed to assess two hypotheses. First, that it is safe to administer the AdcuCD40L vector to individuals with esophageal cancer. Second, that intratumoral administration of the AdCUCD40L vector will induce both the accumulation, in the tumor and in regional lymph nodes, of activated DC, and CD8+ T cells (and other inflammatory cells), including T cells exhibiting tumor-specific responses, as well as systemic antitumor immunity.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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
    • New Jersey
      • Ridgewood, New Jersey, United States, 07450
        • The Valley Hospital
    • New York
      • New York, New York, United States, 10021
        • Weill Medical College of Cornell University

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must be capable of providing informed consent
  • Males and females, age 18 to 75 years
  • Hematocrit > 30%
  • WBC < 10,000
  • Normal prothrombin, partial thromboplastin time; platelet count > 100,000
  • Normal liver-related serum parameters
  • Blood urea nitrogen < 60 mg/dL, creatinine < 2.5 mg/dl
  • No evidence of active infection of any type, including with adenovirus, hepatitis virus (A, B or C) or human immunodeficiency virus
  • No evidence of central nervous system, major psychiatric, musculoskeletal or immune disorder
  • No allergy to the vehicle used to suspend the virus or contrast materials used in radiographic procedures
  • Fertile or infertile individuals; it will be recommended that fertile individuals utilize barrier birth control measures to prevent pregnancy during and for 1 month following the administration of the vector
  • Biopsy proven esophageal cancer; stage IIIB or IV; no chemotherapy for 4 weeks prior to vector dosing; and no chemotherapy or radiation for 4 weeks after vector dosing. Patients must have viable tumor in the esophagus (or gastroesophageal junction). In addition, patients must be (1) be untreated; or, (2) show endoscopic evidence of persistence of disease after treatment with conventional chemotherapy, radiotherapy, or both
  • Individuals not receiving experimental medications or participating in another experimental protocol for at least 4 weeks prior to entry to the study.
  • The study individual must be able to undergo the procedures in the protocol
  • Willingness to participate in the study

Exclusion Criteria:

  • Individuals who do not meet the inclusion criteria will be unable to participate in the protocol
  • Individuals in whom participation in the study would compromise the normal care and expected progression of their disease
  • Individuals receiving corticosteroids or other immunosuppressive medications; previous splenectomy or radiation to the spleen; autoimmune disease
  • Recent (less than 6 wk) cerebral vascular accident
  • Recent (less than 6 wk) transmural myocardial infarction
  • Evidence of infection defined by elevated white blood cell count, temperature > 38.5oC or infiltrate on chest x-ray
  • Cervical esophageal cancer
  • Gastric cancer (tumor more than 50% in the stomach as determined by endoscopy)
  • Lack of viable esophageal tumor (applies only to pretreated patients)
  • Pathology other than squamous cell or adenocarcinoma
  • Malignant ventricular arrhythmia
  • Pregnancy
  • Immunodeficiency disease, including evidence of HIV infection
  • Current alcohol or drug abuse

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: CD40 Gene Transfer
Recruitment will be random from the referral base of the investigators from the popula¬tion of individuals with esophageal cancer defined by the protocol inclu¬sion/exclusion criteria.
Genetic: CD40 Gene Transfer
gene transfer, intratumoral administration
Other Names:
  • CD40 Ligand Gene (AdcuCD40L)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Since this is a dose escalation, phase I design to evaluate toxicity, the analysis for this section will be purely descriptive. Adverse events will be considered on an individual basis.
Time Frame: 8 months
8 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Weill Medical College of Cornell University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2004

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2010

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 22, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 22, 2006

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 24, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 3, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 2, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0011004683
  • 5 R01 CA10198-02 (OTHER_GRANT: National Cancer Institute)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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