Phase 1 Study of the Combination of gp96-Ig Cell Based Lung Cancer Vaccine With Suppression of Adenosinergic Pathways With Theophylline and Oxygen for the Treatment of Non-Small Cell Lung Cancer (NSCLC) Patients With Advanced (Stage IIIB), Relapsed or Metastatic (Stage IV) Disease Who Have Failed Palliative Therapy.
This is a proof of principle trial investigating a heat shock protein gp96 Ig-secreting,
allogeneic tumor cell-vaccine (gp96-Ig vaccine) administered in combination with suppression
of adenosinergic pathways by oxygen and Theophylline to patients with non-small cell lung
cancer (NSCLC). Allogeneic, cultured lung adenocarcinoma cells transfected with HLA A1 and
gp96-Ig will be irradiated and injected intradermally into patients suffering from advanced,
relapsed, or metastatic NSCLC. HLA matching is not required. Safety and immunogenicity of
the combined treatment will be studied in three patient cohorts that will receive twice
monthly, weekly or twice weekly vaccination plus Theophylline and oxygen.
Immune response to vaccination of patients will be measured by determining
adenocarcinoma-specific CD8 CTL precursor frequencies. ELI-spot assay for interferon-y
(IFN-y) will be done to measure cytotoxic function of CD8 cells challenged in vitro with
vaccine cells or autologous tumor cells. Multiparameter flow cytometry of CD8 and CD4 cells
will be carried out to assess functional characteristics and to assess adenosine receptor
levels and expression of hypoxia inducible factor-1alpha.
Patients will be randomized in equal allocation (1:1:1) to one of three dose-schedule (DS)
cohorts defined by the frequency of vaccination. All patients will receive a total course
dose of gp96 vaccine. A total of 36 patients, 12 per DS cohort, will be enrolled. We expect
to accrue at a rate of two patients per month except at the onset of study when successive
enrollment will be spaced to allow observation of first course toxicity in the first several
patients. (See Section 3.3.4 for details.) Patients will be followed for a minimum of one
year, thus study duration is expected to be three years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Adverse Events Experienced by Patients Receiving Study Treatment
Evaluation of the safety of administering a heat shock protein gp96-Ig-secreting allogeneic tumor cell-vaccine (gp96-Ig vaccine) in combination with oxygen and theophylline in patients with advanced NSCLC.
Ikechukwu Akunyili, MD
University of Miami Sylvester Comprehensive Cancer Center
United States: Food and Drug Administration
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