Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy

Phase 1

Terminated

Conditions: Lung Cancer

Interventions: Biological: Allogeneic B7.1/HLA-A1
Other: Placebo

Registration Number: NCT00534209

Lead Sponsor: University of Miami

Brief Summary: 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.

Detailed Description: OUTLINE: This is a multicenter study.

* Phase I (single site \[University of Miami Sylvester Comprehensive Cancer Center\]): Patients receive allogeneic B7.1 and human leukocyte antigen-A1 (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 cluster of differentiation 8 (CD8), cluster of differentiation 4 (CD4), and natural killer cell (NK) response and peripheral blood lymphocytes (PBL) and T helper cell 1 (TH1)/T helper cell 2 (TH2) bias, including levels of interleukin (IL) IL-1β, IL-2, IL-4, IL-5, IL-6, IL-13, Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I: Allogeneic B7.1/HLA-A1	Allogeneic B7.1/HLA-A1	Patients will receive Allogeneic B7.1/HLA-A1 vaccine once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines. Given intradermally.
Arm II: Placebo	Placebo	Patients receive a placebo vaccine intradermally once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.

Primary Outcome Measures

Name	Time	Method
Preliminary Safety Profile (Phase 1)	Up to 13 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 2)	Date of randomization to the earliest date of documented progression.

Secondary Outcome Measures

Name	Time	Method
Correlative Immunological Studies in Study Participants (Phase 2)	Baseline, Week 7 and Week 13	The time course of patients' adaptive immune response to B7 vaccination as compared to control vaccine will be characterized by their CD8, CD4, and NK response (measured by ELI-spots for interferon-gamma (IFN-γ), interleukin 4 (IL-4), and granzyme B secretion) measured prior to vaccination (i.e. at baseline) and over two courses of vaccination (measurements at week 7 and 13).
Safety Profile (Phase 2)	About 13 weeks	The rate 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.
Immune Response (CD8) in B7-vaccinated Participants as Compared to Controls. (Phase 2)	About 13 weeks	Rate of immune response (CD8) in B-7 vaccinated participants reported for measurements taken immediately prior to vaccination (week 0) and throughout the two courses.
Response to Second-line Chemotherapy After Disease Progression (Phase 2)	From Week 1 of Study Therapy until Death or Withdrawal of Consent	The percentage of patients experiencing a clinical response (complete response (CR), partial response (PR), stable disease (SD)) on second-line chemotherapy will be characterized for B7-vaccinated patients and controls.
Relationship of CD8 Response in B7-vaccinated Patients to Their Progression-free Survival.(Phase 2)	From Week 1 of Study Therapy until Death or Withdrawal of Consent	Relationship of CD8 response in B7-vaccinated patients to their progression-free survival. 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).
Overall Survival (Phase 2)	Date of randomization to the recorded date of death	The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that study participants are still alive.

Trial Locations

Locations (2): Memorial Regional Hospital
🇺🇸
Hollywood, Florida, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸
Miami, Florida, United States