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

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

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.

Study Overview

• Status: Unknown
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Biological: aldesleukin; Radiation: radiation therapy; Procedure: adjuvant therapy; Procedure: neoadjuvant therapy; Procedure: conventional surgery

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 260
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70124
    • Recruiting
    • Università degli Studi di Bari
    • Contact: G. Cervellera, MD; Phone Number: 39-080-5478-660
  • Cagliari, Italy, 09042
    • Recruiting
    • Cattedra di Oncologia Medica - Universita degli Studi di Cagliari
    • Contact: P. Puxeddu, MD; Phone Number: 39-070-5109-6253
  • Ferrara, Italy, 44100
    • Recruiting
    • Università di Ferrara
    • Contact: C. Calearo, MD; Phone Number: 39-0532-209-296; Email: ccv@dns.unife.it
  • Florence, Italy, 50134
    • Recruiting
    • Universita Degli Studi di Florence - Policlinico di Careggi
    • Contact: O. Fini-Storchi, MD; Phone Number: 39-55-411739
  • Turin, Italy, 10126
    • Recruiting
    • Università di Torino
    • Contact: G. Valente, MD; Phone Number: 39-011-670-5955
  • Turin, Italy, 10128
    • Recruiting
    • Azienda Sanitaria Ospedaliera Ordine Mauriziano
    • Contact: G. Forni, MD; Phone Number: 39-11-508-1111
  • Vicenza, Italy, 36100
    • Recruiting
    • Ospedale San Bortolo
    • Contact: C. Curioni, MD; Phone Number: 39-444-993-906

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: European Institute of Oncology
• Investigators: Study Chair: Giorgio Cortesina, MD, Universita Degli Studi di Turin

Study record dates

Study Major Dates

• Study Start: September 1, 1992

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 23, 2013
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: stage III squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the oropharynx; stage II squamous cell carcinoma of the lip and oral cavity; stage II squamous cell carcinoma of the oropharynx; tongue cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Aldesleukin
• Other Study ID Numbers: CDR0000064500; CNR-9506; EU-95024