Radiation Therapy in Treating Patients With Metastases to the Lymph Nodes in the Neck From an Unknown Primary Tumor

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase: Completed; Phase 3

Conditions: Carcinoma of Unknown Primary

Treatments: Radiation: radiation therapy

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00047125

CAN-NCIC-EORTC-24001

EORTC-24001-22005

EORTC-24001

DAHANCA-EORTC-24001

RTOG-EORTC-24001

EORTC-22005

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Giving radiation therapy in different ways may kill more tumor cells. It is not yet known which regimen of radiation therapy is more effective in treating patients who have metastases to the lymph nodes in the neck.

PURPOSE: Randomized phase III trial to compare different radiation therapy regimens in treating patients who have metastases to the lymph nodes in the neck from an unknown primary tumor.

Full description

OBJECTIVES:

• Compare the disease-free survival of patients with cervical lymph node metastases of squamous cell carcinoma from an unknown primary treated with selective irradiation vs extensive irradiation.
• Compare the overall survival of patients treated with these regimens.
• Compare the incidence of acute and late side effects in the head and neck region in patients treated with these regimens.
• Compare control of the neck and incidence of subsequent primary in the head and neck region in patients treated with these regimens.
• Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to disease stage (N1-2a vs N2b-3), radiation technique (2D vs 3D conformal vs intensity-modulated), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo selective irradiation of the ipsilateral level of the neck once daily 5 days a week for 6 weeks.
• Arm II: Patients undergo extensive irradiation of the neck (nasopharyngeal, oropharyngeal, hypopharyngeal, and laryngeal mucosa and ipsilateral neck node areas on both sides of the neck) once daily 5 days a week for 6 weeks.

In both arms, treatment continues in the absence of unacceptable toxicity or disease progression.

Quality of life is assessed at baseline, at week 4, on the last day of therapy, and then every 3 months for 1 year.

Patients are followed at day 30, every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 600 patients (300 per treatment arm) will be accrued for this study within 7 years.

Enrollment: 600 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma in cervical lymph node metastasis from an unknown primary tumor

  • Histopathological grade WHO 1-3
  • Pathological stage N1, N2a, N2b, or N3
  • No N2c (i.e., bilateral metastatic nodes)
  • No single node in supraclavicular fossa or submandibular area
  • No evidence of primary tumor in head and neck, lung, esophageal, or other site

• Prior radical, radical modified, or extended radical dissection within the past 8 weeks

  • Selective neck dissection allowed (surgeon must justify why standard procedure was not performed)
  • No node excision alone
  • R0 or R1 disease after dissection

• No distant metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Able and willing to complete quality of life questionnaires
• No other prior or concurrent malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Concurrent chemotherapy allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics

Other

• No other prior therapy for carcinoma of unknown primary except neck dissection

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 2 patient groups

Selective irradiation

Experimental group

Description:

Irradiation of the ipsilateral level I - V of the neck up to a dose of 60 Gy (30x2Gy in 6 weeks).

Treatment:

Radiation: radiation therapy

Extensive irradiation + ipsilaterals levels

Active Comparator group

Description:

Irradiation on the whole mucosa of the larynx, hypopharynx, oropharynx and nasopharynx, and on both sides of the neck (levels I -V) up to a prophylactic dose of 50 Gy (25 x 2 Gy in 5 week).Irradiation of the ipsilateral level I - V of the neck should continue with an additional 10 Gy boost for a total dose of 60 Gy (30 x 2 Gy in 6 weeks).

Treatment:

Radiation: radiation therapy