• Complete response rate [ Designated as safety issue: No ]
  
• Overall response rate [ Designated as safety issue: No ]
  

• Comparison of survival rate between all arms [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• To determine if the combination of autologous dendritic cell-adenovirus p53 vaccine and subsequent chemotherapy (with paclitaxel after progression) will result in a substantial improvement in the clinical response in patients with extensive stage small cell lung cancer.
• To determine if the addition of tretinoin to autologous dendritic cell-adenovirus p53 vaccine improves the objective tumor response rate achieved with the vaccine, by comparing the response to vaccine treatment of patients in arm II to those in arm III.
• To evaluate the survival of all patients enrolled on an intent-to-treat basis, with a comparison made between the three arms.

Secondary

• To determine the frequency of antigen-specific T-cell responses that are induced in the patients over time, with comparisons made between treatment arms II and III.
• To determine the efficacy of tretinoin in reducing the number of immature myeloid cells in patients, by comparing the numbers observed in the peripheral blood of patients in arm II as compared to arm III.

OUTLINE:

• Standard first-line chemotherapy: Patients receive standard first-line chemotherapy comprising 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 4 courses. Patients undergo restaging after completion of first-line chemotherapy.

Patients with progressive disease do not receive any protocol treatment and are changed to second-line therapy.

• Adjuvant therapy: Patients with stable disease or better are then randomized to 1 of 3 arms of adjuvant therapy approximately 3 weeks after completion of first-line chemotherapy.

  • Arm I (Observation only [standard care]): Patients undergo observation with serial CT scans.
  • Arm II (Vaccine): Patients receive autologous dendritic cell-adenovirus p53 vaccine intradermally every 2 weeks for 3 doses. Patients with no sign of disease progression will undergo another leukapheresis and receive autologous dendritic cell-adenovirus p53 vaccine intradermally every 4 weeks for 3 doses.
  • Arm III (Vaccine and tretinoin): Patients receive autologous dendritic cell-adenovirus p53 vaccine for up to 6 doses as in arm II. They also receive oral tretinoin for 3 days before receiving each dose of the vaccine. Patients who develops evidence of disease progression at any point proceed to second-line chemotherapy with paclitaxel once every 21 days in the absence of disease progression or unacceptable toxicity.

All patients undergo blood collection periodically for immunogenic analysis. After completion of study treatment, patients are followed for at least 30 days.