Vaccine Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy

This study has been terminated.
(Per request of Principal Investigator this study was closed.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Miami
ClinicalTrials.gov Identifier:
NCT00534209
First received: September 20, 2007
Last updated: August 13, 2013
Last verified: August 2013

September 20, 2007
August 13, 2013
February 2007
April 2010   (final data collection date for primary outcome measure)
  • Preliminary Safety Profile (Phase I) [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: No ]
  • Preliminary safety profile (Phase I)
  • Progression-free survival (Phase II)
Complete list of historical versions of study NCT00534209 on ClinicalTrials.gov Archive Site
  • 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). ] [ Designated as safety issue: No ]
  • The Adaptive Immune Response [ Time Frame: Reported for measurements taken immediately prior to vaccination (week 0) and throughout the two courses. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: No ]
  • Overall Survival (Phase II) [ Time Frame: Date of randomization to the recorded date of death ] [ Designated as safety issue: No ]
  • Clinical outcomes (Phase I)
  • The adaptive immune response
  • Safety profile (Phase II)
  • Response to second-line chemotherapy after disease progression (Phase II)
  • Overall survival (Phase II)
Not Provided
Not Provided
 
Vaccine Therapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy
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

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.

OBJECTIVES:

PRIMARY OBJECTIVE:

  • 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)

SECONDARY OBJECTIVES:

  • 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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Lung Cancer
  • Biological: Allogeneic B7.1/HLA-A1 transfected tumor cell vaccine
    Dose: At least 4x10^7 irradiated HLA/B7.1 transfected AD100 cells Given intradermally
    Other Names:
    • - B7.1
    • - B7
    • - Ad100-B45-Neo-B7.1-HLA A1 or HLA2
  • Other: Placebo
    Given intradermally
  • Experimental: Arm I

    Patients will receive B7 vaccine once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.

    Given intradermally.

    Intervention: Biological: Allogeneic B7.1/HLA-A1 transfected tumor cell vaccine
  • 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.
    Intervention: Other: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
1
April 2010
April 2010   (final data collection date for primary outcome measure)

INCLUSION CRITERIA

  • Patients with stage IIIB (non-candidates for radiation) or stage IV pathologically confirmed non-small cell carcinoma of the lung that completed 4-6 cycles of platinum based first line chemotherapy and achieved CR, PR or stable disease.
  • Last administration of chemotherapy occurred no later than 4 weeks prior to the enrollment date.
  • ECOG performance status 0-2.
  • Renal Requirements: The calculated creatinine clearance must be at least 50 ml/min.
  • Pulmonary Function Requirements:

    • All patients will undergo evaluation of pulmonary function prior to enrollment.
    • Patients should have a FeV1 more than 30% of the predicted value and/or DLCO more than 30% of the predicted value with a PCO2 < 45mm.
    • Any patient enrolled in the protocol whose respiratory symptoms have experienced marked deterioration not related to a known cause (e.g. pneumonia, CHF or PE) will have request PFT evaluation and if the above parameters are seen will be excluded from the protocol.
  • Age > 18 years.
  • Signed informed consent.
  • Patients should have ANC > 1000/mm3; PLT > 80,000/mm3.

EXCLUSION CRITERIA:

  • Small cell carcinoma of the lung.
  • Existing autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren's disease etc; colitis, inflammatory bowel disease or pancreatitis within 10 years of study.
  • Other active malignancies present within the past three years, except for basal and/or squamous cell carcinoma(s) or in situ cervical cancer.
  • Concomitant steroid or other immunosuppressive therapy.
  • Active infection, or less than 7 days since therapy for acute infections.
  • Pericardial effusion.
  • Currently receiving chemotherapy for another condition (such as arthritis).
  • Time elapsed greater than 4 weeks since last administration of first line chemotherapy for NSCLC.
  • Active or symptomatic cardiac disease such as congestive heart failure, angina pectoris or recent myocardial infarction.
  • Pregnant or lactating women (negative test for pregnancy required of women of childbearing potential).
  • Refusal in fertile men or women to use effective birth control measures during and for six months after the completion of treatment on study.
  • Known HIV infection
  • Untreated or uncontrolled brain metastasis.
  • Liver Enzymes greater than 3 times the institutional upper limit.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00534209
UMIAMI-20057158, SCCC-2005042, WIRB-20051678
Yes
University of Miami
University of Miami
National Cancer Institute (NCI)
Study Chair: Luis E. Raez, MD, FACP University of Miami
University of Miami
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP