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 Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00534209
First received: September 20, 2007
Last updated: July 25, 2014
Last verified: August 2013
  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 transfected tumor cell vaccine
Other: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 Sylvester Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 1
Study Start Date: February 2007
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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
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.
Other: Placebo
Given intradermally

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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 Sylvester Comprehensive Cancer Center
Investigators
Study Chair: Luis E. Raez, MD, FACP University of Miami Sylvester Comprehensive Cancer Center
  More Information

Publications:
Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00534209     History of Changes
Other Study ID Numbers: UMIAMI-20057158, SCCC-2005042, WIRB-20051678
Study First Received: September 20, 2007
Results First Received: January 17, 2013
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 16, 2014