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
18 Years
N/A
Both
Lung Cancer
Trial Information
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
OBJECTIVES:
PRIMARY OBJECTIVE:
- To establish safety of the B7 vaccine when used within 4 weeks of completing first line
platinum based chemotherapy. (Phase I)
- To determine whether patients with advanced non-small cell lung cancer (stages IIIB/IV)
who achieve a clinical response (stable disease, partial response, or complete
response) on first-line platinum-based chemotherapy have an increased time to disease
progression as a result of vaccination with an allogeneic B7.1 and HLA-A1 transfected
tumor-cell vaccine. (Phase II)
SECONDARY OBJECTIVES:
- To evaluate the immune response (CD8) in B7-vaccinated patients as compared to
controls. (Phase II)
- To evaluate the relationship of CD8 response in B7-vaccinated patients with
progression-free survival. (Phase II)
- To evaluate the safety profile of the B7 vaccine. (Phase II)
- To evaluate the response rates on second-line chemotherapy (after disease progression)
in the B7-vaccinated patients as compared to controls. (Phase II)
- To evaluate the overall survival in patients immunized with B7 vaccine as compared to
controls. (Phase II)
- To evaluate the correlative immunological studies. (Phase II)
OUTLINE: This is a multicenter study.
- Phase I (single site [University of Miami Sylvester Comprehensive Cancer Center]):
Patients receive allogeneic B7.1 and 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
CD8, CD4, and NK response and PBL and TH1/TH2 bias, including levels of IL-1β,
IL-2, IL-4, IL-5, IL-6, IL-13, IFN-γ, 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.
Inclusion Criteria
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 CR, PR or stable disease.
- Last administration of chemotherapy occurred no later than 4 weeks prior to the
enrollment date.
- 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 FeV1 more than 30% of the predicted value and/or DLCO
more than 30% of the predicted value with a PCO2 < 45mm.
- Any patient enrolled in the protocol whose respiratory symptoms have experienced
marked deterioration not related to a known cause (e.g. pneumonia, CHF or PE)
will have request PFT evaluation and if the above parameters are seen will be
excluded from the protocol.
- Age > 18 years.
- Signed informed consent.
- Patients should have ANC > 1000/mm3; 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.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
Preliminary Safety Profile (Phase I)
Outcome Description:
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.
Outcome Time Frame:
12 weeks
Safety Issue:
Yes
Principal Investigator
Luis E. Raez, MD, FACP
Investigator Role:
Study Chair
Investigator Affiliation:
University of Miami Sylvester Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
EPROST-20057158
NCT ID:
NCT00534209
Start Date:
February 2007
Completion Date:
April 2010
Related Keywords:
- Lung Cancer
- stage IIIB non-small cell lung cancer
- stage IV non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| University of Miami Sylvester Comprehensive Cancer Center | Miami, Florida 33136 |
| Memorial Regional Hospital | Hollywood, Florida 33021 |
