Vaccine Therapy in Patients With Stages IIIB/IV Non-Small Cell Lung Cancer Who Have Finished First-Line Chemotherapy

NCT ID: NCT00534209

Last Updated: 2017-10-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2010-04-30

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.

Conditions

Lung Cancer

Keywords

stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Allogeneic B7.1/HLA-A1

Intervention Type: BIOLOGICAL

Dose: At least 4x10\^7 irradiated HLA/B7.1 transfected AD100 cells Given intradermally

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Given intradermally

Interventions

Allogeneic B7.1/HLA-A1

Dose: At least 4x10\^7 irradiated HLA/B7.1 transfected AD100 cells Given intradermally

Intervention Type: BIOLOGICAL

Placebo

Given intradermally

Intervention Type: OTHER

Other Intervention Names

- B7.1; - B7; - Ad100-B45-Neo-B7.1-HLA A1 or HLA2

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luis E. Raez, MD, FACP

Role: STUDY_CHAIR

University of Miami Sylvester Comprehensive Cancer Center

Locations

Memorial Regional Hospital

Hollywood, Florida, United States

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 14605671 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15461522 (View on PubMed)

Other Identifiers

SCCC-2005042

Identifier Type: OTHER

Identifier Source: secondary_id

WIRB-20051678

Identifier Type: OTHER

Identifier Source: secondary_id

20057158

Identifier Type: -

Identifier Source: org_study_id