Surgery and Radiation Therapy With or Without Interleukin-2 in Treating Patients With Cancer of the Mouth or Oropharynx

Study Overview
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Brief Summary
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RATIONALE: Interleukin-2 may stimulate a person's white blood cells to kill cancer cells of the mouth or oropharynx. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not known whether giving interleukin-2 with surgery and radiation therapy is more effective than surgery and radiation therapy alone. PURPOSE: This randomized phase III trial is studying surgery and radiation therapy alone to see how well they work compared to surgery, radiation therapy, and interleukin-2 in treating patients with cancer of the mouth or oropharynx.

Detailed Description
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OBJECTIVES: Compare the disease-free and overall survival in patients with previously untreated squamous cell carcinoma of the oral cavity or oropharynx treated with resection with or without and neoadjuvant and adjuvant perilymphatic interleukin-2 (IL-2) and radiotherapy. Compare the response rate in patients treated with these regimens. Determine the local and systemic effects of locoregional IL-2 on host-tumor interaction and immune properties in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and tumor stage (T2, N0-2 vs T2, N3 or T3-4, N0-3). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo induction comprising interleukin-2 (IL-2) via perilymphatic injections to the ipsilateral myelohyoid muscle and insertion of the sternocleidomastoid muscle on days 1-5 and 8-12. Within 10 days after the last IL-2 injection, patients undergo en bloc resection of the primary tumor and corresponding lymphatic drainage area and pre-study margins. Beginning within 4 weeks after surgery, patients with T2, N0-3 disease but with pathohistological evidence of node invasion or capsular rupture of node metastasis or T3-4, N0-3 disease undergo adjuvant radiotherapy 5 days a week for 4.5-6.5 weeks. Beginning within 4 weeks after surgery or radiotherapy (if applicable), patients receive adjuvant IL-2 via perilymphatic injections to the contralateral myelohyoid muscle and insertion of the sternocleidomastoid muscle on days 1-5. Adjuvant IL-2 continues monthly for at least 1 year in the absence of disease progression. Arm II: Patients undergo resection and radiotherapy (if eligible) as in arm I. Patients are followed monthly for 1 year and then every 2 months for 2 years. PROJECTED ACCRUAL: A total of 260 patients (130 per treatment arm) will be accrued for this study.

Official Title
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Multicentre Randomised Trial of Inductive and Adjuvant Perilymphatically Injected Proleukin (rlL-2) in The Treatment of Operable Primary Squamous Cell Carcinoma of The Oral Cavity and Oropharynx

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Biological: aldesleukin
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven squamous cell carcinoma of the oral cavity or oropharynx Operable, primary, unilateral, stage T2-4, N0-3, M0 disease No high probability of bilateral lymphatic spread (requirement for bilateral neck dissection) No tumor involvement of the following sites: Pterygopalatine fossa Carotid artery Maxillary sinus Facial skin Anterior floor of the mouth Base of the tongue infiltrating more than 1 cm Measurable or evaluable disease by physical exam and/or noninvasive imaging PATIENT CHARACTERISTICS: Age: 75 and under Performance status: ECOG 0-2 OR Karnofsky 70-100% Life expectancy: More than 3 months Hematopoietic: WBC at least 4,000/mm3 Platelet count at least 60,000/mm3 Hematocrit at least 30% Hepatic: Bilirubin normal Hepatitis B surface antigen negative Renal: Creatinine normal Cardiovascular: No congestive heart failure No uncontrolled hypertension No coronary artery disease No serious arrhythmia No evidence of prior myocardial infarction on ECG (stress test required if in doubt) Other: HIV negative No autoimmune disease No contraindications to pressor agents No serious infection requiring antibiotics No other concurrent primary malignancy Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy: No prior or other concurrent immunotherapy Chemotherapy: No prior or concurrent chemotherapy Endocrine therapy: No prior or concurrent hormonal therapy No concurrent corticosteroids Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics No prior major organ allografts Other: No other prior therapy No other concurrent investigational drugs, agents, or devices No concurrent nonsteroidal antiinflammatory drugs, ranitidine, cimetidine, or coumarin

Ages Eligible for Study
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Maximum Age: 75 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: aldesleukin|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival at 3 and 5 years |  |  | 
| Recurrence/metastasis rate at 3 and 5 years |  |  | 
| Response rate |  |  | 
| Local and systemic effects of treatment |  |  | 

 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, tongue cancer