Vaccine Therapy and Chemotherapy With or Without Tretinoin in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Condition(s) targeted: Lung Cancer

Intervention: autologous dendritic cell-adenovirus p53 vaccine (Biological); tretinoin (Drug); observation (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: H. Lee Moffitt Cancer Center and Research Institute

Official(s) and/or principal investigator(s):
Alberto Chiappori, MD, Study Chair, Affiliation: H. Lee Moffitt Cancer Center and Research Institute

RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as carboplatin, etoposide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Tretinoin may help lung cancer cells become more like normal cells and grow and spread more slowly. Giving vaccine therapy together with combination chemotherapy, with or without tretinoin, may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving vaccine therapy and combination chemotherapy together with or without tretinoin works in treating patients with extensive-stage small cell lung cancer.

Official title: A Randomized Phase II Trial Using Dendritic Cells Transduced With an Adenoviral Vector Containing the p53 Gene to Immunize Patients With Extensive Stage Small Cell Lung Cancer in Combination With Chemotherapy With or Without All Trans Retinoic Acid

Study design: Treatment, Randomized

Primary outcome:

Complete response rate

Overall response rate

Secondary outcome:

Comparison of survival rate between all arms

Toxicity

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed extensive stage small cell lung cancer (SCLC)

- No uncontrolled CNS metastases

PATIENT CHARACTERISTICS:

Inclusion criteria:

- ECOG performance status 0-2

- WBC > 3,000/mm³

- ANC > 1,500/mm³

- Platelets > 100,000/mm³

- Hematocrit > 25%

- Bilirubin < 2. 0 mg/dL

- Creatinine < 2. 0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

Exclusion criteria:

- Serious ongoing infection

- Other pre-existing immunodeficiency condition including known HIV infection

- Known pre-existing autoimmune disorder

- History of a second malignancy within the past 5 years, except nonmelanoma skin

cancer

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

- At least 2 weeks since prior radiotherapy

- At least 4 weeks since prior and no concurrent steroid therapy

- No anticipated requirement for chronic steroids at the time of vaccination

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa, Florida 33612-9497, United States; Recruiting
Clinical Trials Office - H. Lee Moffitt Cancer Center and Rese, Phone: 800-456-7121, Email: canceranswers@moffitt.org

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: July 2007
Last updated: February 6, 2009