A Phase I-II Trial Using Dendritic Cells Transduced With An Adenoviral Vector Containing The p53 Gene To Immunize Patients With Extensive Stage Small Cell Lung Cancer After Standard Chemotherapy
- Determine the maximum tolerated dose of autologous dendritic cell-adenovirus p53
vaccine, administered after standard chemotherapy, in patients with extensive stage
small cell lung cancer.
- Determine the toxicity of this regimen in these patients.
- Determine the development of an anti-p53-specific immune response in these patients
after treatment with this regimen.
- Determine the tumor response rate, time to progression, and overall survival of
patients treated with this regimen.
- Determine the frequency of anti-adenovirus immune responses in these patients after
treatment with this regimen.
OUTLINE: This is a dose-escalation study of autologous dendritic cell-adenovirus p53
Patients undergo leukapheresis and dendritic cells are cultured. Adenovirus carrying p53
gene particles are added to the dendritic cells to make the vaccine. Leukapheresis is
performed before chemotherapy or 8 weeks after the last dose of chemotherapy if the patient
has already started chemotherapy.
Patients receive standard chemotherapy before receiving the vaccine. The recommended regimen
is carboplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3. Treatment
repeats every 21 days for up to 6 courses in the absence of disease progression or
Patients with progressive disease (PD) at 6 weeks after chemotherapy are removed from the
Patients are followed at day 140 and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 43-58 patients (3-18 for phase I and 40 for phase II) will be
accrued for this study within 3 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Rate of Toxicity of the Ad-p53 DC Vaccine
To evaluate the toxicity of the Ad-p53 dendritic cell (DC) vaccine. While there is no expected toxicity from the Ad-p53 vaccine, there may be unforeseen adverse effects. Patients will be monitored for toxicity, particularly for evidence of autoimmunity. Complete blood counts (CBCs) to monitor for hematologic toxicity, serum creatinine to monitor for renal toxicity, liver function tests (LFTs) to monitor for hepatic toxicity, and a standard clinical toxicity will be performed every other week throughout the period of immunization. In addition, a medical history and physical examination will be performed on a monthly basis.
Scott J. Antonia, M.D., Ph.D.
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|