Vaccine Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy
RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells.
PURPOSE: This randomized phase I/II trial is studying the side effects of vaccine therapy and to see how well it works in treating patients with stage IIIB or stage IV non-small cell lung cancer who have finished first-line chemotherapy.
|Lung Cancer||Biological: Allogeneic B7.1/HLA-A1 transfected tumor cell vaccine Other: Placebo||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:||Phase I/II Clinical Trial of Immunotherapy With an Allogeneic B7.1/HLA-A1 Transfected Tumor Cell Vaccine in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer That Have Completed First Line Chemotherapy|
- Preliminary Safety Profile (Phase I) [ Time Frame: 12 weeks ]This will include the number of patients experiencing toxicity over the course of treatment, characterized by type of toxicity and grade, and by the time of toxicity onset in relation to day of vaccination.
- Progression-free Survival (Phase II) [ Time Frame: Date of randomization to the earliest date of documented progression. ]
- Clinical Outcomes (Phase I) [ Time Frame: Summarized by the median and range of follow up time for patients grouped according to disease status (progression/no progression) and vital status (died/alive at last contact). ]
- The Adaptive Immune Response [ Time Frame: Reported for measurements taken immediately prior to vaccination (week 0) and throughout the two courses. ]
- Safety Profile (Phase II) [ Time Frame: The number of patients experiencing toxicity over the course of treatment will be characterized by type of toxicity and grade, and by the time of toxicity onset in relation to day of vaccination. ]
- Response to Second-line Chemotherapy After Disease Progression (Phase II) [ Time Frame: TThe percentage of patients experiencing a clinical response (CR, PR, SD) on second-line chemotherapy will be characterized for B7-vaccinated patients and controls. ]
- Overall Survival (Phase II) [ Time Frame: Date of randomization to the recorded date of death ]
|Study Start Date:||February 2007|
|Study Completion Date:||April 2010|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients will receive B7 vaccine once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.
Biological: Allogeneic B7.1/HLA-A1 transfected tumor cell vaccine
Dose: At least 4x10^7 irradiated HLA/B7.1 transfected AD100 cells Given intradermally
Placebo Comparator: Arm II
Patients receive a placebo vaccine intradermally once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.
- To establish safety of the B7 vaccine when used within 4 weeks of completing first line platinum based chemotherapy. (Phase I)
- To determine whether patients with advanced non-small cell lung cancer (stages IIIB/IV) who achieve a clinical response (stable disease, partial response, or complete response) on first-line platinum-based chemotherapy have an increased time to disease progression as a result of vaccination with an allogeneic B7.1 and HLA-A1 transfected tumor-cell vaccine. (Phase II)
- To evaluate the immune response (CD8) in B7-vaccinated patients as compared to controls. (Phase II)
- To evaluate the relationship of CD8 response in B7-vaccinated patients with progression-free survival. (Phase II)
- To evaluate the safety profile of the B7 vaccine. (Phase II)
- To evaluate the response rates on second-line chemotherapy (after disease progression) in the B7-vaccinated patients as compared to controls. (Phase II)
- To evaluate the overall survival in patients immunized with B7 vaccine as compared to controls. (Phase II)
- To evaluate the correlative immunological studies. (Phase II)
OUTLINE: This is a multicenter study.
- Phase I (single site [University of Miami Sylvester Comprehensive Cancer Center]): Patients receive allogeneic B7.1 and HLA-A1 transfected tumor cell vaccine intradermally (ID) in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses. If no more than 1 of 6 patients experience a probable or definitively treatment related adverse effect (i.e., grade 2 autoimmune or grade 3-4 of any type), patients proceed to the phase II portion of the study. If 2 or more (out of 6) patients experience treatment related adverse effects the study stops.
Phase II (randomized): Patients are stratified according to study site (University of Miami Sylvester Comprehensive Cancer Center or Memorial Regional Hospital), type of prior first-line treatment (platinum and taxane vs platinum and gemcitabine), and presence of brain metastasis (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive allogeneic B7.1 and HLA-A1 transfected tumor cell vaccine ID in weeks 1, 3, and 5. Treatment repeats every 6 weeks for 2 courses.
- Arm II: Patients receive a placebo vaccine as in arm I. Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed for CD8, CD4, and NK response and PBL and TH1/TH2 bias, including levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-13, IFN-γ, TNF-α via ELISA.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 4 years, and then once a year thereafter.
PROJECTED ACCRUAL: A total of 66 patients (6 patients for phase I and 60 patients for phase II) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00534209
|United States, Florida|
|Memorial Regional Hospital|
|Hollywood, Florida, United States, 33021|
|University of Miami Sylvester Comprehensive Cancer Center|
|Miami, Florida, United States, 33136|
|Study Chair:||Luis E. Raez, MD, FACP||University of Miami Sylvester Comprehensive Cancer Center|