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

European Institute of Oncology

Status and phase: Unknown; Phase 3

Conditions: Head and Neck Cancer

Treatments: Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Radiation: radiation therapy; Biological: aldesleukin; Procedure: conventional surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT00002702

EU-95024

CNR-9506

CDR0000064500

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 260 estimated patients

Sex: All

Ages: Under 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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