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
18 Years
75 Years
Both
Esophageal Neoplasms
Trial Information
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
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.
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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Outcome Measure:
Expression of CD40L and cytokines
Outcome Time Frame:
5-15 days
Safety Issue:
No
Principal Investigator
Ronald G. Crystal, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Department of Genetic Medicine
Authority:
United States: Food and Drug Administration
Study ID:
0502007770
NCT ID:
NCT00504322
Start Date:
July 2011
Completion Date:
July 2011
Related Keywords:
- Esophageal Neoplasms
- Esophageal Neoplasms
- Neoplasms
- Carcinoma
- Esophageal Diseases
- Esophageal Neoplasms
Name | Location |
|---|---|
| Weill Medical College of Cornell University | New York, New York 10021 |
| The Valley Hospital | Paramus, New Jersey 07652 |
