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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00002702
• Other study ID #: CDR0000064500
• Secondary ID: CNR-9506EU-95024
• Status: Recruiting
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: August 23, 2013
• Start date: September 1992

Study information

• Verified date: February 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 75 Years

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• aldesleukin

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Italy	Universita Degli Studi di Bari	Bari
Italy	Cattedra di Oncologia Medica - Universita degli Studi di Cagliari	Cagliari
Italy	Universita di Ferrara	Ferrara
Italy	Universita Degli Studi di Florence - Policlinico di Careggi	Florence
Italy	Azienda Sanitaria Ospedaliera Ordine Mauriziano	Turin
Italy	Universita di Torino	Turin
Italy	Ospedale San Bortolo	Vicenza

Sponsors (1)

Lead Sponsor	Collaborator
European Institute of Oncology

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival at 3 and 5 years			No
Primary	Recurrence/metastasis rate at 3 and 5 years			No
Primary	Response rate			No
Primary	Local and systemic effects of treatment			No