Vaccine Therapy in Treating Patients Who Are Undergoing Surgery for Stage IB, Stage II, or Stage IIIA Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a person's tumor cells and white blood cells may make the body build an effective immune response to kill tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients who are undergoing surgery for stage IB, stage II, or stage IIIA non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of adjuvant autologous dendritic cells loaded with irradiated autologous tumor cells in patients with stage IB-IIIA non-small cell lung cancer undergoing resection. Determine the safety and tolerability of this vaccine in these patients. Secondary Determine the feasibility of this vaccine in these patients. Determine vaccine-specific and antitumor immunity in patients treated with this vaccine. OUTLINE: This is a dose-escalation study. Patients undergo leukaphersis to isolate peripheral blood mononuclear cells (PBMC). PBMC are expanded ex vivo to generate monocyte-derived dendritic cells (DC). Autologous tumor cells are harvested and purified at the time of surgical resection. DC are then loaded with irradiated autologous tumor cells. Within 4-8 weeks after surgical resection, patients receive autologous DC loaded with irradiated autologous tumor cells intradermally on approximately days 1, 30, and 60 in the absence of unacceptable toxicity. Cohorts of 6-9 patients receive escalating doses of vaccine until the maximum tolerated dose (MTD) is determined. If 2 of 9 patients in the first cohort experience dose-limiting toxicity, that dose level is considered the MTD. Patients are followed at approximately 1 and 4 months, and then every 6 months for 4 years. PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 18 months.

Official Title
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A Phase I Clinical Trial of Mature Autologous Dendritic Cells Loaded With Irradiated Autologous Tumor Cells for the Treatment of Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: autologous tumor cell vaccine
* Drug: therapeutic autologous dendritic cells
* Procedure: adjuvant therapy
* Procedure: biological therapy
* Procedure: conventional surgery
* Procedure: surgery
* Procedure: tumor cell derivative vaccine
* Procedure: vaccine therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of non-small cell lung cancer Clinical stage IB-IIIA disease Candidate for surgical resection as primary treatment for tumor Surgically resectable tumor ≥ 2.0 cm in diameter No brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Platelet count ≥ 100,000/mm^3 WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Hematocrit ≥ 30% Hepatic Hepatitis B surface antigen negative* Hepatitis B core antigen negative* Hepatitis C virus negative* Bilirubin ≤ 2.0 mg/dL AST and ALT ≤ 2 times upper limit of normal NOTE: *Screening performed only if liver enzymes are elevated Renal Creatinine ≤ 2.2 mg/dL BUN ≤ 40 mg/dL Pulmonary FEV_1 > 2.0 L (pre-resection) OR Predicted post-resection FEV_1 > 1.0 L No more than 2 chronic obstructive pulmonary disease exacerbations requiring > 2 weeks of oral steroids and/or hospitalization within the past year Immunologic Purified protein derivative (PPD) skin test negative HIV-1 and HIV-2 negative No acute infection, including any acute viral, bacterial, or fungal infection requiring specific therapy within the past 7 days No allergy to study agents No known autoimmune or collagen vascular disorder Other Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix No underlying condition that would preclude study therapy PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent anti-tumor necrosis factor agents Chemotherapy Standard adjuvant chemotherapy for lung cancer allowed provided therapy is completed ≥ 30 days before administration of the first study vaccine No concurrent cyclophosphamide Endocrine therapy No concurrent high-dose corticosteroids (e.g., > 10 mg of prednisone) Concurrent corticosteroids for minor breathing exacerbations allowed provided patient receives ≤ 2 short courses (≤ 10 days per course) within a 45-day period No concurrent corticosteroids within 48 hours before or after study vaccine administration Radiotherapy Standard adjuvant radiotherapy for lung cancer allowed provided therapy is completed ≥ 30 days before administration of the first study vaccine Surgery No prior organ allograft Other No concurrent antihistamines within 48 hours before or after study vaccine administration No concurrent cimetidine or other H2 blockers within 48 hours before or after study vaccine administration Concurrent antibiotics for minor infection allowed provided patient receives ≤ 2 short courses (≤ 10 days per course) within a 45-day period No concurrent cyclosporine No concurrent azathioprine No other concurrent drugs known to significantly alter immune function No concurrent cytotoxic therapy No concurrent participation in another clinical trial involving experimental therapy No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: autologous tumor cell vaccine|nan|
|Drug: therapeutic autologous dendritic cells|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: biological therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: surgery|nan|
|Procedure: tumor cell derivative vaccine|nan|
|Procedure: vaccine therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer