Trials / Withdrawn
WithdrawnNCT01799161
Combination of gp96-Ig Vaccine, Theophylline and Oxygen for the Treatment of Patients With Advanced, Relapsed or Metastatic Non-Small Cell Lung Cancer
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.
- Status
- Withdrawn
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 0 (actual)
- Sponsor
- Eckhard Podack · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
NSCLC tumors are appropriate targets for active immunotherapy, because they are non-immunogenic, which indicates that NSCLC does not stimulate a spontaneous immune response. NSCLC tumor-secreted gp96-Ig is an ideal vaccine because it combines adjuvant activity with polyvalent peptide specificity. Tumor secreted gp96 activates dendritic cells (DC), natural killer cells (NK) and cytotoxic T lymphocytes (CTL). Tumor cells can be killed by NK-specific mechanisms, by promiscuous killing of CD8 CTL through NKG2D, and by MHC restricted CD8 CTL activity. The activation of DC and NK by tumor secreted gp96 may also counteract the generation of immuno-suppressive CD4 regulatory cells. Suppression of adenosinergic pathways by oxygen and theophylline in combination with immunotherapy will improve tumor rejection. Allogeneic, gp96-Ig secreting tumor cells used as vaccine are expected to generate NK and CTL with activity to the patient's autologous tumor.
Detailed description
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.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| BIOLOGICAL | gp96-Ig Vaccine | |
| DRUG | Theophylline | 300 mg capsule daily of Theophylline during 1st course, then adjusted dose |
| OTHER | Oxygen | 24-hr oxygen delivered via nasal cannula or oxygen mask during 1st course, then adjusted dose. |
| PROCEDURE | Immunologic Evaluation | Frequency of IFN-y,CD8 cells in response to vaccine in available tumor samples Blood draw to assess immunological response \[frequency of CD4+, FoxP3 (Treg), et al\] in treated patients. |
Timeline
- Start date
- 2014-12-01
- Primary completion
- 2018-04-01
- First posted
- 2013-02-26
- Last updated
- 2014-11-17
Source: ClinicalTrials.gov record NCT01799161. Inclusion in this directory is not an endorsement.