gp96-Ig Cell Based Lung Cancer Vaccine with Theophylline and Oxygen for Advanced Non-Small Cell Lung Cancer
This study aims to evaluate the safety of using a gp96-Ig cell based lung cancer vaccine in combination with theophylline and oxygen for treating advanced non-small cell lung cancer, by observing the number of adverse events experienced by patients.
gp96-Ig Vaccine
+ Theophylline
+ Oxygen
Bronchial Neoplasms+7
+ Carcinoma, Bronchogenic
+ Lung Diseases
Treatment Study
Summary
Study start date: December 1, 2014
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria: Histologically confirmed NSCLC (squamous, adeno-, large cell anaplastic, bronchoalveolar, and non-small cell carcinoma NOS): stage IIIB with malignant pleural effusion, stage IV, or recurrent disease. 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: Active or symptomatic cardiac disease such as congestive heart failure, angina pectoris or recent myocardial infarction. Patients with history of these conditions who are stable taking cardiac medications will also be excluded. 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.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.3 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
Active ComparatorGroup II
Active ComparatorGroup III
Active ComparatorStudy Objectives
Primary Objectives
Secondary Objectives