- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00534209
Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OUTLINE: This is a multicenter study.
- Phase I (single site [University of Miami Sylvester Comprehensive Cancer Center]): Patients receive allogeneic B7.1 and human leukocyte antigen-A1 (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 cluster of differentiation 8 (CD8), cluster of differentiation 4 (CD4), and natural killer cell (NK) response and peripheral blood lymphocytes (PBL) and T helper cell 1 (TH1)/T helper cell 2 (TH2) bias, including levels of interleukin (IL) IL-1β, IL-2, IL-4, IL-5, IL-6, IL-13, Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
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Hollywood, Florida, United States, 33021
- Memorial Regional Hospital
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Miami, Florida, United States, 33136
- University of Miami Sylvester Comprehensive Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 complete response (CR), partial response (PR) or stable disease.
- Last administration of chemotherapy occurred no later than 4 weeks prior to the enrollment date.
- Eastern Cooperative Oncology Group (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 Forced expiratory volume in 1 second (FEV1) more than 30% of the predicted value and/or Diffusing capacity (DLCO) more than 30% of the predicted value with a partial pressure of carbon dioxide (PCO2) < 45mm.
- Any patient enrolled in the protocol whose respiratory symptoms have experienced marked deterioration not related to a known cause (e.g. pneumonia, congestive heart failure (CHF) or pulmonary embolism (PE)) will have request pulmonary function test (PFT) evaluation and if the above parameters are seen will be excluded from the protocol.
- Age ≥ 18 years.
- Signed informed consent.
- Patients should have absolute neutrophil count (ANC) ≥ 1000/mm3; platelets (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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I: Allogeneic B7.1/HLA-A1
Patients will receive Allogeneic B7.1/HLA-A1 vaccine once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines. Given intradermally. |
Dose: At least 4x10^7 irradiated HLA/B7.1 transfected AD100 cells Given intradermally
Other Names:
|
Placebo Comparator: Arm II: Placebo
Patients receive a placebo vaccine intradermally once every other week for 2 courses over 12 weeks, for a maximum of 6 vaccines.
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Given intradermally
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Preliminary Safety Profile (Phase 1)
Time Frame: Up to 13 weeks
|
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.
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Up to 13 weeks
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Progression-free Survival (Phase 2)
Time Frame: Date of randomization to the earliest date of documented progression.
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Date of randomization to the earliest date of documented progression.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immune Response (CD8) in B7-vaccinated Participants as Compared to Controls. (Phase 2)
Time Frame: About 13 weeks
|
Rate of immune response (CD8) in B-7 vaccinated participants reported for measurements taken immediately prior to vaccination (week 0) and throughout the two courses.
|
About 13 weeks
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Relationship of CD8 Response in B7-vaccinated Patients to Their Progression-free Survival.(Phase 2)
Time Frame: From Week 1 of Study Therapy until Death or Withdrawal of Consent
|
Relationship of CD8 response in B7-vaccinated patients to their progression-free survival.
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).
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From Week 1 of Study Therapy until Death or Withdrawal of Consent
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Safety Profile (Phase 2)
Time Frame: About 13 weeks
|
The rate 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.
|
About 13 weeks
|
Response to Second-line Chemotherapy After Disease Progression (Phase 2)
Time Frame: From Week 1 of Study Therapy until Death or Withdrawal of Consent
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The percentage of patients experiencing a clinical response (complete response (CR), partial response (PR), stable disease (SD)) on second-line chemotherapy will be characterized for B7-vaccinated patients and controls.
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From Week 1 of Study Therapy until Death or Withdrawal of Consent
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Overall Survival (Phase 2)
Time Frame: Date of randomization to the recorded date of death
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The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that study participants are still alive.
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Date of randomization to the recorded date of death
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Correlative Immunological Studies in Study Participants (Phase 2)
Time Frame: Baseline, Week 7 and Week 13
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The time course of patients' adaptive immune response to B7 vaccination as compared to control vaccine will be characterized by their CD8, CD4, and NK response (measured by ELI-spots for interferon-gamma (IFN-γ), interleukin 4 (IL-4), and granzyme B secretion) measured prior to vaccination (i.e. at baseline) and over two courses of vaccination (measurements at week 7 and 13).
|
Baseline, Week 7 and Week 13
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Luis E. Raez, MD, FACP, University of Miami Sylvester Comprehensive Cancer Center
Publications and helpful links
General Publications
- Raez LE, Cassileth PA, Schlesselman JJ, Padmanabhan S, Fisher EZ, Baldie PA, Sridhar K, Podack ER. Induction of CD8 T-cell-Ifn-gamma response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma. Cancer Gene Ther. 2003 Nov;10(11):850-8. doi: 10.1038/sj.cgt.7700641.
- Frankowski DJ, Raez J, Manners I, Winnik MA, Khan SA, Spontak RJ. Formation of dispersed nanostructures from poly(ferrocenyldimethylsilane-b-dimethylsiloxane) nanotubes upon exposure to supercritical carbon dioxide. Langmuir. 2004 Oct 12;20(21):9304-14. doi: 10.1021/la049646l.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20057158
- SCCC-2005042 (Other Identifier: UM/Sylvester Comprehensive Cancer Center)
- WIRB-20051678 (Other Identifier: Western IRB (WIRB))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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