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Efficacy Study on the Transfer of Adenovirus With the CD40 Ligand Gene (AdcuCD40L) to Patients With Esophageal Carcinoma (cd40)

Primary Purpose

Esophageal Neoplasms

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
AdcuCD40L
Placebo
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Esophageal Neoplasms focused on measuring Esophageal Neoplasms

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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; clinically stage I-III, deemed resectable by the patient's surgeon. No history of neoadjuvant chemotherapy or chemoradiotherapy. Distant metastases are to be ruled out at the discretion of the physician treating the patient according to standards of care
  • 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 week) cerebral vascular accident
  • Recent (less than 6 week) 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)
  • Pathology other than squamous cell or adenocarcinoma
  • Malignant ventricular arrhythmia
  • Pregnancy
  • Immunodeficiency disease, including evidence of HIV infection
  • Current alcohol or drug abuse
  • Esophageal tumor too small for adequate tissue harvest (determined during esophagoscopy at the time of vector or placebo injection)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Active Comparator

    Arm Label

    placebo

    AdcuCD40L

    Arm Description

    The placebo will be the salt water-sugar solution used as a vehicle for the vector.

    Using Weill-IRB protocol #0011004683 dose escalation study to determine the highest non-toxic dose of the AdcuCD40L vector, this dose (likely 10^11 particle units) will be used for all individuals enrolled in this efficacy study. Since there is no evidence that delay of surgery for solid tumors for 15 days following diagnosis alters the prognosis, surgery for removal of the primary tumor will be carried out at either 5 or 15 days after administration of the vector (n= 12/group, including n=6 receiving the AdcuCD40L vector, and n=6 receiving placebo). This will permit assessment of the resulting data (in a randomized, blinded fashion) and the biologic responses to the AdCUCD40L vector over time.

    Outcomes

    Primary Outcome Measures

    Expression of CD40L and cytokines

    Secondary Outcome Measures

    Full Information

    First Posted
    July 19, 2007
    Last Updated
    May 3, 2016
    Sponsor
    Weill Medical College of Cornell University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00504322
    Brief Title
    Efficacy Study on the Transfer of Adenovirus With the CD40 Ligand Gene (AdcuCD40L) to Patients With Esophageal Carcinoma
    Acronym
    cd40
    Official Title
    Phase II, Randomized, Double-blinded, Placebo-Control, Toxicity/Efficacy Study on the Transfer of Adenovirus With the CD40 Ligand Gene (AdcuCD40L) to Patients With Stage I, II or III Esophageal Carcinoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2016
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    No funding available.
    Study Start Date
    July 2011 (undefined)
    Primary Completion Date
    July 2011 (Actual)
    Study Completion Date
    July 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Weill Medical College of Cornell University

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This study is a randomized, double-blinded assessment of biologic efficacy of AdcuCD40L. The individuals enrolled in this study will be individuals with biopsy proven resectable esophageal carcinoma. The dose of the AdcuCD40L vector (administered endoscopically directly to the tumor) will be the highest tolerable dose (most likely 10^11 particle units) determined from Weill-IRB protocol #0011004683 dose escalation study.
    Detailed Description
    This study is designed to add to the safety profile data as well as assessing biologic efficacy parameters. It will include 24 individuals with biopsy proven, resectable, stage I-III esophageal cancer. Because there may be immune responses attributable to the gene therapy vector itself, independent of the CD40L transgene, this part of the study is designed in a randomized, blinded fashion to compare intratumoral administration of the AdcuCD40L vector compared to a placebo. Because there are likely differences over time in the pattern of the biologic response to the expression of CD40L in the tumor (including activation and trafficking of DC, and recruitment and activation of immune cells), this study will include 2 "time" cohorts (based on the time between administration of the AdcuCD40L vector and the time of surgery to remove the tumor). Using Weill-IRB protocol #0011004683 dose escalation study to determine the highest non-toxic dose of the AdcuCD40L vector, this dose (likely 10^11 particle units) will be used for all individuals enrolled in this efficacy study. The placebo will be the salt water-sugar solution used as a vehicle for the vector. Since there is no evidence that delay of surgery for solid tumors for 15 days following diagnosis alters the prognosis, surgery for removal of the primary tumor will be carried out at either 5 or 15 days after administration of the vector (n= 12/group, including n=6 receiving the AdcuCD40L vector, and n=6 receiving placebo). This will permit assessment of the resulting data (in a randomized, blinded fashion) and the biologic responses to the AdCUCD40L vector over time. In addition to safety/toxicity parameters, the primary tumor, regional and distant nodes removed at the time of surgery, and peripheral blood will be assessed for biologic parameters relevant to responses to the AdcuCD40L vector.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Esophageal Neoplasms
    Keywords
    Esophageal Neoplasms

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    placebo
    Arm Type
    Placebo Comparator
    Arm Description
    The placebo will be the salt water-sugar solution used as a vehicle for the vector.
    Arm Title
    AdcuCD40L
    Arm Type
    Active Comparator
    Arm Description
    Using Weill-IRB protocol #0011004683 dose escalation study to determine the highest non-toxic dose of the AdcuCD40L vector, this dose (likely 10^11 particle units) will be used for all individuals enrolled in this efficacy study. Since there is no evidence that delay of surgery for solid tumors for 15 days following diagnosis alters the prognosis, surgery for removal of the primary tumor will be carried out at either 5 or 15 days after administration of the vector (n= 12/group, including n=6 receiving the AdcuCD40L vector, and n=6 receiving placebo). This will permit assessment of the resulting data (in a randomized, blinded fashion) and the biologic responses to the AdCUCD40L vector over time.
    Intervention Type
    Genetic
    Intervention Name(s)
    AdcuCD40L
    Other Intervention Name(s)
    Active Comparator
    Intervention Description
    Using Weill-IRB protocol #0011004683 dose escalation study to determine the highest non-toxic dose of the AdcuCD40L vector, this dose (likely 10^11 particle units) will be used for all individuals enrolled in this efficacy study. Since there is no evidence that delay of surgery for solid tumors for 15 days following diagnosis alters the prognosis, surgery for removal of the primary tumor will be carried out at either 5 or 15 days after administration of the vector (n= 12/group, including n=6 receiving the AdcuCD40L vector, and n=6 receiving placebo). This will permit assessment of the resulting data (in a randomized, blinded fashion) and the biologic responses to the AdCUCD40L vector over time.
    Intervention Type
    Genetic
    Intervention Name(s)
    Placebo
    Other Intervention Name(s)
    salt water-sugar solution
    Intervention Description
    The placebo will be the salt water-sugar solution used as a vehicle for the vector.
    Primary Outcome Measure Information:
    Title
    Expression of CD40L and cytokines
    Time Frame
    5-15 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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; clinically stage I-III, deemed resectable by the patient's surgeon. No history of neoadjuvant chemotherapy or chemoradiotherapy. Distant metastases are to be ruled out at the discretion of the physician treating the patient according to standards of care 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 week) cerebral vascular accident Recent (less than 6 week) 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) Pathology other than squamous cell or adenocarcinoma Malignant ventricular arrhythmia Pregnancy Immunodeficiency disease, including evidence of HIV infection Current alcohol or drug abuse Esophageal tumor too small for adequate tissue harvest (determined during esophagoscopy at the time of vector or placebo injection)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Ronald G. Crystal, MD
    Organizational Affiliation
    Department of Genetic Medicine
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

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