We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Vaccine Therapy in Patients With Stages IIIB/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:
ClinicalTrials.gov Identifier:
NCT00534209
First Posted: September 24, 2007
Last Update Posted: October 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
University of Miami
  Purpose

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.


Condition Intervention Phase
Lung Cancer Biological: Allogeneic B7.1/HLA-A1 Other: Placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (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

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Preliminary Safety Profile (Phase 1) [ Time Frame: 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) [ Time Frame: Date of randomization to the earliest date of documented progression. ]

Secondary Outcome Measures:
  • Immune Response (CD8) in B7-vaccinated Participants as Compared to Controls. (Phase 2) [ Time Frame: 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.

  • Relationship of CD8 Response in B7-vaccinated Patients to Their Progression-free Survival.(Phase 2) [ Time Frame: 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).

  • Safety Profile (Phase 2) [ Time Frame: 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.

  • Response to Second-line Chemotherapy After Disease Progression (Phase 2) [ Time Frame: 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.

  • Overall Survival (Phase 2) [ Time Frame: 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.

  • Correlative Immunological Studies in Study Participants (Phase 2) [ Time Frame: 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).


Enrollment: 1
Actual Study Start Date: January 2009
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I: 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.

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

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 complete response (CR), partial response (PR) or stable disease.
  • Last administration of chemotherapy occurred no later than 4 weeks prior to the enrollment date.
  • Eastern Cooperative Oncology Group (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 Forced expiratory volume in 1 second (FEV1) more than 30% of the predicted value and/or Diffusing capacity (DLCO) more than 30% of the predicted value with a partial pressure of carbon dioxide (PCO2) < 45mm.
    • Any patient enrolled in the protocol whose respiratory symptoms have experienced marked deterioration not related to a known cause (e.g. pneumonia, congestive heart failure (CHF) or pulmonary embolism (PE)) will have request pulmonary function test (PFT) evaluation and if the above parameters are seen will be excluded from the protocol.
  • Age ≥ 18 years.
  • Signed informed consent.
  • Patients should have absolute neutrophil count (ANC) ≥ 1000/mm3; platelets (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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00534209


Locations
United States, Florida
Memorial Regional Hospital
Hollywood, Florida, United States, 33021
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Investigators
Study Chair: Luis E. Raez, MD, FACP University of Miami Sylvester Comprehensive Cancer Center
  More Information

Publications:
Responsible Party: University of Miami
ClinicalTrials.gov Identifier: NCT00534209     History of Changes
Other Study ID Numbers: 20057158
SCCC-2005042 ( Other Identifier: UM/Sylvester Comprehensive Cancer Center )
WIRB-20051678 ( Other Identifier: Western IRB (WIRB) )
First Submitted: September 20, 2007
First Posted: September 24, 2007
Results First Submitted: January 17, 2013
Results First Posted: February 20, 2013
Last Update Posted: October 16, 2017
Last Verified: September 2017

Keywords provided by University of Miami:
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Vaccines
Immunologic Factors
Physiological Effects of Drugs