Clinical trial NCT00534209: Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Keywords: stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2007-09-24
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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 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.

Primary outcomes:
measure: Preliminary Safety Profile (Phase 1)
timeFrame: Up to 13 weeks
measure: Progression-free Survival (Phase 2)
timeFrame: Date of randomization to the earliest date of documented progression.
Secondary outcomes:
measure: Immune Response (CD8) in B7-vaccinated Participants as Compared to Controls. (Phase 2)
timeFrame: About 13 weeks
measure: Relationship of CD8 Response in B7-vaccinated Patients to Their Progression-free Survival.(Phase 2)
timeFrame: From Week 1 of Study Therapy until Death or Withdrawal of Consent
measure: Safety Profile (Phase 2)
timeFrame: About 13 weeks
measure: Response to Second-line Chemotherapy After Disease Progression (Phase 2)
timeFrame: From Week 1 of Study Therapy until Death or Withdrawal of Consent
measure: Overall Survival (Phase 2)
timeFrame: Date of randomization to the recorded date of death
measure: Correlative Immunological Studies in Study Participants (Phase 2)
timeFrame: Baseline, Week 7 and Week 13
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
Study officials:
affiliation: University of Miami Sylvester Comprehensive Cancer Center
name: Luis E. Raez, MD, FACP
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.