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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00504322
Recruitment Status : Withdrawn (No funding available.)
First Posted : July 20, 2007
Last Update Posted : May 4, 2016
Sponsor:
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Tracking Information
First Submitted Date  ICMJE July 19, 2007
First Posted Date  ICMJE July 20, 2007
Last Update Posted Date May 4, 2016
Study Start Date  ICMJE July 2011
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2015)
Expression of CD40L and cytokines [ Time Frame: 5-15 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 19, 2007)
  • numbers of activated DC and other relevant immune cells
  • levels of expression of genes coding for relevant immune mediators
  • the numbers of T cells exhibiting tumor-specific immunity
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy Study on the Transfer of Adenovirus With the CD40 Ligand Gene (AdcuCD40L) to Patients With Esophageal Carcinoma
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Esophageal Neoplasms
Intervention  ICMJE
  • Genetic: AdcuCD40L
    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.
    Other Name: Active Comparator
  • Genetic: Placebo
    The placebo will be the salt water-sugar solution used as a vehicle for the vector.
    Other Name: salt water-sugar solution
Study Arms  ICMJE
  • Placebo Comparator: placebo
    The placebo will be the salt water-sugar solution used as a vehicle for the vector.
    Intervention: Genetic: Placebo
  • Active Comparator: AdcuCD40L
    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: Genetic: AdcuCD40L
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: December 16, 2015)
0
Original Estimated Enrollment  ICMJE
 (submitted: July 19, 2007)
24
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00504322
Other Study ID Numbers  ICMJE 0502007770
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Weill Medical College of Cornell University
Study Sponsor  ICMJE Weill Medical College of Cornell University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ronald G. Crystal, MD Department of Genetic Medicine
PRS Account Weill Medical College of Cornell University
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP