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

NCT00328887 | Withdrawn Phase 1 DMC

• 2 other identifiers: 00110046835 R01 CA10198-02
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Esophageal Neoplasms

Keywords

Esophageal Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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.

  8 months

Study Arms (1)

CD40 Gene Transfer

EXPERIMENTAL

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

Interventions

CD40 Gene Transfer GENETIC

gene transfer, intratumoral administration

Also known as: CD40 Ligand Gene (AdcuCD40L)

CD40 Gene Transfer

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

The Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

CD40 Ligand

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Tumor Necrosis Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Membrane Proteins; Biological Factors

Study Officials

• Ronald G Crystal, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2006
• First Posted: May 24, 2006
• Study Start: November 1, 2004
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: May 3, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)