PEG-interferon Alfa-2b in Treating Patients With Stage II, Stage III, or Stage IV Head and Neck Cancer That Can Be Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: SCH 54031 (PEG-interferon alfa-2b) may interfere with the growth of tumor cells and slow the growth of head and neck cancer. It may also stop the growth of head and neck cancer by blocking blood flow to the tumor. Giving PEG-interferon alfa-2b before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This randomized phase II trial is studying how well different doses of PEG-interferon alfa-2b work in treating patients with stage II, stage III, or stage IV head and neck cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the antiangiogenic effects of PEG-interferon alfa-2b, in terms of pre- and post-treatment levels of microvessel density (MVD), endothelial cell apoptosis, vascular endothelial growth factor (VEGF), interleukin-8, basic fibroblast growth factor (bFGF), Nuclear Factor-KappaB (NF-KB), matrix metalloproteinase/MMP-9, and NF-KB in biopsy specimens, from patients with resectable stage II-IV squamous cell carcinoma of the head and neck. Secondary Determine the toxicity profile of this drug in these patients. Determine the clinical response in patients treated with this drug. OUTLINE: This is a randomized, controlled study. Patients are randomized to 1 of 4 treatment arms. Arm I: Patients undergo surgery within 3 weeks after randomization. Arm II: Patients receive PEG-interferon alfa-2b subcutaneously on days 1, 8, and 15. Arm III: Patients receive PEG-interferon alfa-2b as in arm II but at a higher dose. Arm IV: Patients receive PEG-interferon alfa-2b as in arm II but at a higher dose than in arm III. In arms II, III, and IV, patients undergo surgery within 1 week after completion of PEG-interferon alfa-2b. After completion of study treatment, patients are followed for up to 30 days. PROJECTED ACCRUAL: A maximum of 72 patients will be accrued for this study.

Official Title
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A Randomized Phase II Study of SCH 54031 in Surgically Resectable Squamous Cell Tumors of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: PEG-interferon alfa-2b
* Procedure: Conventional surgery
* Procedure: Neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the head and neck Stage II, III, or IV disease One of the following primary tumor sites: Oral cavity Oropharynx Hypopharynx Larynx Resectable disease Scheduled to undergo surgery as primary treatment Distant metastases or a second primary tumor allowed provided tumor deemed resectable by the surgeon No squamous cell carcinoma of the nasopharynx or skin PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 White Blood Cells (WBC) > 3,000/mm^3 Platelet count ≥ 150,000/mm^3 Hemoglobin ≥ 10 g/dL Transfusion and/or epoetin alfa support allowed provided it is given ≥ 1 week before study entry AND the patient is stable Bilirubin < 1.5 times upper limit of normal (ULN) serum glutamic pyruvic transaminase (SGPT) ≤ 5 times ULN Creatinine < 1.5 times ULN No hemolytic anemia No hemoglobinopathies (e.g., thalassemia) No prior or current ascites No bleeding varices No other evidence of decompensated liver disease No symptomatic ischemic heart disease No symptomatic congestive heart failure No other uncontrolled heart condition No chronic obstructive pulmonary disease No documented pulmonary hypertension No other chronic pulmonary disease No known HIV positivity No AIDS-related illness No active uncontrolled infection No immunologically mediated disease, including any of the following: Inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) Rheumatoid arthritis Idiopathic thrombocytopenia purpura Systemic lupus erythematosus Autoimmune hemolytic anemia Scleroderma Severe psoriasis No Central Nervous System (CNS) trauma No confusion or disorientation No active seizure disorders requiring medication No spontaneous encephalopathy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No pre-existing uncontrolled thyroid abnormality No poorly controlled diabetes mellitus No history of major psychiatric illness that would prelude giving informed consent No nonmalignant systemic disease that would preclude study participation PRIOR CONCURRENT THERAPY: More than 4 weeks since prior biologic therapy and recovered More than 4 weeks since prior chemotherapy and recovered More than 4 weeks since prior radiotherapy and recovered More than 4 weeks since prior surgery No prior interferon No other concurrent immunotherapy No concurrent chemotherapy No concurrent hormonal antineoplastic therapy No concurrent systemic corticosteroids No concurrent radiotherapy

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>Control (no treatment), conventional surgery. | Procedure: Conventional surgery<br>* Participants on the control arm may undergo surgery at anytime within 3 weeks of randomization, and those randomized to PEG-Intron will undergo surgery on Days 16-22 following initiation of treatment.<br>Procedure: Neoadjuvant therapy<br> <br> |
| Experimental: PEG-Intron 0.5 mg/kg<br>PEG-interferon alfa-2b 0.5 mg/kg subcutaneously (SQ) once a week for 3 weeks, plus surgery. | Biological: PEG-interferon alfa-2b<br>* Study medication begins on Day 1 and taken subcutaneously once each week with the last dose being taken within 1 week prior to surgery or biopsy.<br>* Other names: SCH 54031;Procedure: Conventional surgery<br>* Participants on the control arm may undergo surgery at anytime within 3 weeks of randomization, and those randomized to PEG-Intron will undergo surgery on Days 16-22 following initiation of treatment.<br>Procedure: Neoadjuvant therapy<br> <br> |
| Experimental: PEG-Intron 2.5 mg/kg<br>PEG-interferon alfa-2b 2.5 mg/kg SQ once a week for 3 weeks, plus surgery. | Biological: PEG-interferon alfa-2b<br>* Study medication begins on Day 1 and taken subcutaneously once each week with the last dose being taken within 1 week prior to surgery or biopsy.<br>* Other names: SCH 54031;Procedure: Conventional surgery<br>* Participants on the control arm may undergo surgery at anytime within 3 weeks of randomization, and those randomized to PEG-Intron will undergo surgery on Days 16-22 following initiation of treatment.<br>Procedure: Neoadjuvant therapy<br> <br> |
| Experimental: PEG-Intron 5.0 mg/kg<br>PEG-interferon Alfa-2b 5 mg/kg SQ once a week for 3 weeks, plus surgery. | Biological: PEG-interferon alfa-2b<br>* Study medication begins on Day 1 and taken subcutaneously once each week with the last dose being taken within 1 week prior to surgery or biopsy.<br>* Other names: SCH 54031;Procedure: Conventional surgery<br>* Participants on the control arm may undergo surgery at anytime within 3 weeks of randomization, and those randomized to PEG-Intron will undergo surgery on Days 16-22 following initiation of treatment.<br>Procedure: Neoadjuvant therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | 3 weeks following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage II squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, stage II squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the lip and oral cavity, recurrent squamous cell carcinoma of the oropharynx