S0122: Combination Chemotherapy, Radiation Therapy, and Vaccine Therapy in Limited-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use 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. Vaccines may make the body build an immune response to kill tumor cells. Combining chemotherapy and radiation therapy with vaccine therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy and radiation therapy with vaccine therapy in treating patients who have limited-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Determine the efficacy of cisplatin, etoposide, and thoracic radiotherapy followed by cisplatin, etoposide, monoclonal antibody 11D10 anti-idiotype vaccine (TriAb), and monoclonal antibody GD2 anti-idiotype vaccine (TriGem), in terms of overall and progression-free survival of patients with limited stage small cell lung cancer. Determine the immune response to each of the 2 anti-idiotype vaccines when used in this regimen in these patients. Determine the qualitative and quantitative toxicity of this regimen in these patients. Determine the response rates (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with this regimen. OUTLINE: This is a multicenter study. Induction therapy: Patients receive cisplatin IV over 1 hour on days 1, 8, 29, and 36 and etoposide IV over 1 hour on days 1-5 and 29-33. Thoracic radiotherapy is administered 5 days a week, beginning on day 1 of chemotherapy, for 5 weeks. Patients then undergo radiotherapy boost for 1.5 weeks. Patients with stable disease or at least partial response proceed to consolidation therapy. Consolidation therapy (begins within 3-5 weeks of the last dose of induction chemotherapy or radiotherapy): Patients receive cisplatin IV over 1 hour on day 1 and etoposide IV over 1 hour on days 1-3 of weeks 11 and 14. Patients also receive monoclonal antibody 11D10 anti-idiotype vaccine (TriAb) and monoclonal antibody GD2 anti-idiotype vaccine (TriGem) intradermally on day 1 of weeks 11, 13, 15, and 17 (4 injections) and then monthly subcutaneously for 2 years. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response after consolidation chemotherapy undergo cranial radiotherapy 5 days a week for 3 weeks. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 18 months.

Official Title
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A Phase II Trial of Patients With Limited Stage Small Cell Lung Cancer Treated With Thoracic Radiation Therapy and Chemotherapy With Cisplatin/Etoposide Followed by Cisplatin/Etoposide and Anti-Idiotype Monoclonal Antibody Vaccines

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: monoclonal antibody 11D10 anti-idiotype vaccine
* Biological: monoclonal antibody GD2 anti-idiotype vaccine
* Drug: cisplatin
* Drug: etoposide
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed limited stage small cell lung cancer (SCLC) Evidence of disease by CT scan of the chest Measurable or evaluable disease outside of area of prior surgical resection No malignant pericardial or pleural effusions (cytologically positive effusions or exudative effusions not attributable to other etiologies) No CNS disease by chest CT scan or MRI PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Not specified Renal Creatinine no greater than upper limit of normal OR Creatinine clearance at least 60 mL/min Other No prior hypersensitivity or contraindication to monoclonal antibody 11D10 anti-idiotype vaccine (TriAb), monoclonal antibody GD2 anti-idiotype vaccine (TriGem), or aluminum hydroxide No known sensitivity to rodent proteins (i.e., anti-OKT-3, ONCOSCINT scan) No grade 1 or greater symptomatic sensory neuropathy No other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer in complete remission, or any other cancer for which patient has been disease free for 5 years If significant clinical hearing loss already present, must accept risk of further hearing loss Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy No prior biologic therapy for SCLC No prior TriAb or TriGem No prior murine antibodies No prior mouse proteins At least 30 days since prior immunotherapy At least 30 days since any prior immunization Chemotherapy No prior systemic chemotherapy for SCLC No concurrent cyclophosphamide or methotrexate Endocrine therapy At least 30 days since prior systemic corticosteroids No concurrent systemic corticosteroids (except as an antiemetic) Radiotherapy No prior radiotherapy to the thorax or neck region No concurrent intensity modulated radiotherapy Surgery See Disease Characteristics At least 2 weeks since prior thoracic or other major surgery and recovered Other At least 30 days since prior investigational agents or devices No other concurrent investigational agents No other concurrent immunosuppressants (e.g., cyclosporine) No concurrent chronic systemic antihistamines No concurrent amifostine

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cisplatin and etoposide followed by vaccine<br>standard chemotherapy with cisplatin and etoposide followed by cisplans and etoposide with an anti-idiotype monoclonal antibody vaccine | Biological: monoclonal antibody 11D10 anti-idiotype vaccine<br> <br> Biological: monoclonal antibody GD2 anti-idiotype vaccine<br> <br> Drug: cisplatin<br> <br> Drug: etoposide<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | time from date of registration to date of death | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immune response | T-cell proliferation and HAMA testing | at Week 10 | 
| toxicity assessment | assessment of qualitative and quantitative toxicities | 22 weeks | 
| response | RECIST partial and complete response | 25 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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limited stage small cell lung cancer