Vaccine Therapy, Chemotherapy, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed With Surgery

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Vaccines made from a gene-modified virus may make the body build an immune response to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high energy x-rays to damage tumor cells. Combining vaccine therapy with chemotherapy and radiation therapy may kill more tumor cells. PURPOSE: This clinical trial is studying how well giving vaccine therapy together with paclitaxel, carboplatin, and radiation therapy works in treating patients with stage III non-small cell lung cancer that cannot be removed with surgery.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the safety and feasibility of standard paclitaxel, carboplatin, and radiotherapy in combination with vaccinia-CEA-TRICOM vaccine, fowlpox-CEA-TRICOM vaccine, and recombinant fowlpox GM-CSF vaccine in patients with unresectable stage III non-small cell lung cancer. Secondary Determine clinical response in patients treated with this regimen. Determine time to disease progression and overall median survival of patients treated with this regimen. Determine immunologic response in patients treated with this regimen. OUTLINE: This is a pilot study. Vaccine: Patients receive vaccinia-CEA-TRICOM vaccine subcutaneously (SC) on day 0 and fowlpox-CEA-TRICOM (rF-CEA-TRICOM) vaccine SC on days 14, 29, 43, 57, 70, 91, and 112. Patients also receive recombinant fowlpox GM-CSF (rF-GM-CSF) vaccine SC with each vaccination. Patients with stable or responding disease after day 112 continue to receive rF-CEA-TRICOM and rF-GM-CSF SC every 3 weeks in the absence of disease progression or unacceptable toxicity. Radiotherapy: Patients undergo radiotherapy on days 21-25, 28-32, 35-39, 42-46, 49-53, 56-60, and 63-67. Chemotherapy: Concurrently with radiotherapy, patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 21, 28, 35, 42, 49, 56, and 63. Patients also receive paclitaxel and carboplatin on days 91 and 112 (after completion of radiotherapy). Patients are followed annually for up to 15 years. PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 4-6 months.

Official Title
-----------------
A Pilot Trial of a CEA/TRICOM-Based Vaccine in Combination With Combined Chemotherapy/Radiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Biological: recombinant fowlpox GM-CSF vaccine adjuvant
* Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine
* Biological: recombinant vaccinia-CEA(6D)-TRICOM vaccine
* Drug: carboplatin
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed non-small cell lung cancer Stage III (locally advanced) disease Unresectable disease Carcinoembryonic antigen (CEA)-positive (staining ≥ 20% of cells) tumor by immunohistochemistry HLA-A2-positive No distant metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy At least 6 months Hematopoietic Granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Absolute lymphocyte count ≥ 600/mm^3 Hemoglobin ≥ 10 g/dL Hepatic Bilirubin < 1.5 mg/dL AST ≤ 2 times upper limit of normal Hepatitis B and C negative Renal Creatinine normal OR Creatinine clearance > 60 mL/min Cardiovascular No unstable or newly diagnosed angina pectoris No myocardial infarction within the past 6 months No New York Heart Association class II-IV congestive heart failure Immunologic HIV negative No altered immune function No active or history of eczema No atopic dermatitis No autoimmune disease, including any of the following: Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia Systemic lupus erythematosus Sjögren's syndrome Scleroderma Myasthenia gravis Goodpasture's syndrome Addison's disease Hashimoto's thyroiditis Active Graves' disease Multiple sclerosis No known history of allergy or serious reaction to prior vaccination with vaccina No known allergy to eggs No active or history of extensive psoriasis, severe acneiform rash, impetigo, varicella zoster, burns, or other traumatic or pruritic skin condition Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 4 months after study participation No history of seizures or encephalitis Able to avoid close household contact with the following individuals for at least 3 weeks after vaccinia vaccination: Children under 3 years of age Pregnant or nursing women Individuals with a history of or active eczema or other eczematoid skin disorders Individuals with other acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, impetigo, burns, varicella zoster, severe acne, or other open rashes or wounds) Immunodeficient or immunosuppressed individuals, including HIV-positive persons, by disease or therapy No other active malignancy within the past 2 years No other concurrent serious illness PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 years since prior immunotherapy with related vaccinia and fowlpox vaccines At least 3 years since prior antigen-specific peptides No other concurrent immunotherapy Chemotherapy No prior paclitaxel or carboplatin for lung cancer At least 3 years since prior chemotherapy No other concurrent chemotherapy Endocrine therapy No concurrent steroids, except for any of the following: Topical steroids Inhaled steroids for mild or moderate asthma Dexamethasone as premedication for paclitaxel OR for short-term doses (48-72 hours in duration) to control refractory nausea that is not responding to other antiemetics Systemic corticosteroids for ≥ grade 3 radiation pneumonitis No steroid eye-drops for at least 3 weeks after vaccinia vaccination No concurrent hormonal therapy No concurrent systemic glucocorticoids Radiotherapy No prior radiotherapy to the lung fields No prior thoracic radiotherapy for lung cancer No other concurrent radiotherapy Surgery Surgical scars must be healed No prior splenectomy No concurrent major surgical procedure Other Recovered from all prior therapy No other concurrent anticancer agent or therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: recombinant fowlpox GM-CSF vaccine adjuvant|nan|
|Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine|nan|
|Biological: recombinant vaccinia-CEA(6D)-TRICOM vaccine|nan|
|Drug: carboplatin|nan|
|Drug: paclitaxel|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

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

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