Efficacy Study on the Transfer of Adenovirus With the CD40 Ligand Gene (AdcuCD40L) to Patients With Esophageal Carcinoma - Full Text View

Sponsors and Collaborators:	Weill Medical College of Cornell University National Cancer Institute (NCI)
Information provided by:	Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT00504322

Purpose

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.

Condition	Intervention	Phase
Esophageal Neoplasms	Genetic: AdcuCD40L	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: CD40 Ligand

U.S. FDA Resources

Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:

Expression of CD40L and cytokines [ Time Frame: 5-15 days ] [ Designated as safety issue: No ]
Cellular infiltrate characterization [ Time Frame: 5-15 days ] [ Designated as safety issue: No ]
Levels of AdCUCD40L [ Time Frame: 5-15 days ] [ Designated as safety issue: No ]
Tumor cell apoptosis [ Time Frame: 5-15 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	July 2009
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator	Genetic: AdcuCD40L salt water-sugar solution used as a vehicle for the vector
2: Active Comparator	Genetic: AdcuCD40L gene transfer, intratumoral administration

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504322

Contacts

Contact: Charleen Hollmann, RN, MPA, PhD

646-962-2672

chollman@med.cornell.edu

Locations

United States, New Jersey
The Valley Hospital
Ridgewood, New Jersey, United States, 07450
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10021

Sponsors and Collaborators

Weill Medical College of Cornell University

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Ronald G. Crystal, MD

Department of Genetic Medicine

More Information

No publications provided

Responsible Party:	Genetic Medicine, Weill Cornell Medical College ( Ronald Crystal, MD )
Study ID Numbers:	0502007770
Study First Received:	July 19, 2007
Last Updated:	May 27, 2009
ClinicalTrials.gov Identifier:	NCT00504322 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:

Esophageal Neoplasms

Study placed in the following topic categories:

Digestive System Neoplasms
Digestive System Diseases
Esophageal Disorder
Gastrointestinal Diseases
Head and Neck Neoplasms
Esophageal Neoplasms

Adenoviridae Infections
Gastrointestinal Neoplasms
Esophageal Cancer
Esophageal Diseases
Carcinoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases

Head and Neck Neoplasms
Esophageal Neoplasms
Gastrointestinal Neoplasms
Esophageal Diseases

ClinicalTrials.gov processed this record on September 11, 2009