Combination of gp96-Ig Vaccine, Theophylline and Oxygen for the Treatment of Patients With Advanced, Relapsed or Metastatic Non-Small Cell Lung Cancer
NCT ID: NCT01799161
Last Updated: 2014-11-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE1
INTERVENTIONAL
2014-12-31
Brief Summary
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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
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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
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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DS-1
6 week course of gp96 Vaccine: \>= 4 x 10\^7 cells twice monthly on Day 1. Up to 3 courses, 9 vaccinations.
gp96-Ig Vaccine
Theophylline
300 mg capsule daily of Theophylline during 1st course, then adjusted dose
Oxygen
24-hr oxygen delivered via nasal cannula or oxygen mask during 1st course, then adjusted dose.
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.
DS-2
6 week course of gp96 Vaccine: \>= 2 x 10\^7 cells weekly on Day 1. Up to 3 courses, 18 vaccinations.
gp96-Ig Vaccine
Theophylline
300 mg capsule daily of Theophylline during 1st course, then adjusted dose
Oxygen
24-hr oxygen delivered via nasal cannula or oxygen mask during 1st course, then adjusted dose.
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.
DS-3
6 week course of gp96 Vaccine: \>= 1 x 10\^7 cells twice weekly on Days 1 and 4. Up to 3 courses, 36 vaccinations.
gp96-Ig Vaccine
Theophylline
300 mg capsule daily of Theophylline during 1st course, then adjusted dose
Oxygen
24-hr oxygen delivered via nasal cannula or oxygen mask during 1st course, then adjusted dose.
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.
Interventions
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gp96-Ig Vaccine
Theophylline
300 mg capsule daily of Theophylline during 1st course, then adjusted dose
Oxygen
24-hr oxygen delivered via nasal cannula or oxygen mask during 1st course, then adjusted dose.
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* At least one site of measurable disease.
* Brain metastasis if present and treated must be stable by CT scan or MRI for at least 4 weeks after treatment.
* Patient must have received and failed at least one line of palliative therapy (chemotherapy or biological therapy)
* Age \>= 18 years.
* ECOG performance status 0-2.
* Life expectancy \>= 3 months.
* Laboratory parameters
* Hemoglobin levels \>= 10.0 (transfusions allowed if necessary).
* ANC \>= 1,500.
* Platelets \>= 100k.
* Creatinine clearance \>= 50 ml/min.
* Total and direct bilirubin: \< 3.0 x upper institution limit for normal.
* Liver function tests: AST, ALT, and AlkP \< 3.0 x upper institution limit for normal.
* Signed informed consent.
Exclusion Criteria
* Pregnant or lactating women (negative test for pregnancy is required of women of childbearing potential).
* Known HIV infection.
* Uncontrolled or untreated brain or spinal cord metastases.
* Active infection.
* Concomitant steroid or other immunosuppressive therapy.
* Other active malignancies present within the past three years, except for basal and/or squamous cell carcinoma(s) or in situ cervical cancer.
* Meningeal carcinomatosis.
* Chemotherapy, radiation therapy, or other anti-tumor therapy during the last three weeks.
* Immune deficiency syndromes, including the following: rheumatoid arthritis, systemic lupus erythematousus, Sjogren's disease, sarcoidosis, vasculitis, polymyositis, glomerulonephritis.
* Compromised lung function:
* FeV1 \< 30% of the predicted value, or
* DLCO \< 30% of the predicted value, or
* PCO2 \> 45 mmHg.
18 Years
ALL
No
Sponsors
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Eckhard Podack
OTHER
Responsible Party
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Eckhard Podack
Professor
Principal Investigators
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Ikechukwu Akunyili, MD
Role: PRINCIPAL_INVESTIGATOR
University of Miami
Other Identifiers
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20110847
Identifier Type: -
Identifier Source: org_study_id