Clinical trial NCT00002702: Surgery and Radiation Therapy With or Without Interleukin-2 in Treating Patients With Cancer of the Mouth or Oropharynx
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 260
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Disease-free survival at 3 and 5 years
measure: Recurrence/metastasis rate at 3 and 5 years
measure: Response rate
measure: Local and systemic effects of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Universita Degli Studi di Bari
city: Cagliari
country: Italy
facility: Cattedra di Oncologia Medica - Universita degli Studi di Cagliari
city: Ferrara
country: Italy
facility: Universita di Ferrara
city: Florence
country: Italy
facility: Universita Degli Studi di Florence - Policlinico di Careggi
city: Turin
country: Italy
facility: Universita di Torino
city: Turin
country: Italy
facility: Azienda Sanitaria Ospedaliera Ordine Mauriziano
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
Study officials:
affiliation: Universita Degli Studi di Turin
name: Giorgio Cortesina, MD
role: STUDY_CHAIR
References: