Clinical trial NCT00002476: Radiation Therapy With or Without Chemotherapy in Treating Patients With Advanced Head and Neck Cancer
Official title: Phase III Randomized Study of Radiotherapy Alone vs With Concurrent Chemotherapy With MTX or VBMF (VCR/BLEO/MTX/5-FU) vs Subsequent Chemotherapy vs Concurrent and Subsequent Chemotherapy in Patients With Advanced Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: stage II squamous cell carcinoma of the lip and oral cavity
stage II verrucous carcinoma of the oral cavity
stage III squamous cell carcinoma of the lip and oral cavity
stage III verrucous carcinoma of the oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV verrucous carcinoma of the 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
stage II squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
stage II squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage II squamous cell carcinoma of the larynx
stage II verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
stage II squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-06-09
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if radiation therapy plus chemotherapy is more effective than radiation therapy alone in treating patients with advanced head and neck cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without chemotherapy in treating patients with advanced head and neck cancer.

Detailed description: OBJECTIVES: I. Determine whether the addition of methotrexate (MTX) or VBMF (vincristine/bleomycin/methotrexate/fluorouracil) to radiotherapy for advanced carcinoma of the head and neck (with or without primary surgery) influences locoregional control and prolongs survival. II. Determine whether an effect on locoregional control or survival is apparent when chemotherapy is given during or following radiotherapy and whether it is increased when chemotherapy is given at both times. III. Determine, in a special randomization of patients with cancer of the oral cavity or oropharynx, whether neck irradiation improves locoregional control and survival.

OUTLINE: Randomized study. Patients without prior surgery are randomized 1:2 to Arms I:II-IV, while those with prior surgery are randomized 1:1 between Arms I and II only. Patients with tumors of the oral cavity or oropharynx may elect additional randomization between Arms V and VI and will receive irradiation of the primary according to the Manchester regimen. Arm I: Radiotherapy. Irradiation of the primary and/or lymph nodes according to 1 of 2 regimens (Manchester 3-week schedule or SECOG 6-week schedule) using megavoltage equipment. Arm II: Radiotherapy plus Concurrent Single-agent or 4-Drug Combination Chemotherapy with Leucovorin Rescue. Involved-field irradiation as in Arm I; plus Methotrexate, MTX, NSC-740; with Leucovorin calcium, CF, NSC-3590; or VBMF: Vincristine, VCR, NSC-67574; Bleomycin, BLEO, NSC-125066; MTX; Fluorouracil, 5-FU, NSC-19893; with CF. Arm III: Radiotherapy plus Subsequent Single-agent or 4-Drug Combination Chemotherapy with Leucovorin Rescue. Involved-field irradiation as in Arm I; plus MTX or VBMF; with CF. Arm IV: Radiotherapy plus Concurrent and Subsequent Single-agent or 4-Drug Combination Chemotherapy with Leucovorin Rescue. Involved-field irradiation as in Arm I; plus MTX or VBMF; with CF. Arm V: Radiotherapy. Neck node irradiation using megavoltage equipment. Arm VI: Observation. No nodal irradiation.

PROJECTED ACCRUAL: At least 1,000 patients will be entered.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically confirmed squamous cell cancer of the head and neck suitable for treatment with radiotherapy T2, T3, or T4 primary lesions Any N No distant metastasis May also be anaplastic carcinoma, verrucous carcinoma, or transitional cell carcinoma (as of 1/97) No occult primaries (as of 1/97) No adenocarcinomas, lymphomas, or melanomas (as of 1/97) Synchronous head and neck tumors are eligible (tumor with the worse prognosis is entered into study) (as of 1/97) Patients receiving surgery to neck nodes only must be randomized as surgery patients (as of 1/97) Patients with tumors of the oral cavity or oropharynx may additionally elect randomization to nodal irradiation vs. no further therapy provided there is no second primary

PATIENT CHARACTERISTICS: Age: 75 and under for patients electing participation in the nodal vs. no nodal irradiation portion of the study Performance status: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Fit for any protocol treatment option Willing to receive any protocol treatment option Prior malignancy allowed provided the treating clinician considers the patient cured

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior therapy Chemotherapy: No prior therapy Endocrine therapy: No prior therapy Radiotherapy: No prior therapy Surgery: Prior biopsy or excision allowed

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Indore
country: India
facility: Raj Tilak
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
state: England
city: London
country: United Kingdom
facility: Middlesex Hospital- Meyerstein Institute
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend General Hospital
state: England
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
state: Northern Ireland
city: Belfast
country: United Kingdom
facility: Belfast City Hospital Trust
state: Northern Ireland
Study officials:
affiliation: University College London Hospitals
name: Jeffrey S. Tobias, MD
role: STUDY_CHAIR
References:
citation: Tobias JS, Monson K, Gupta N, Macdougall H, Glaholm J, Hutchison I, Kadalayil L, Hackshaw A; UK Head and Neck Cancer Trialists' Group. Chemoradiotherapy for locally advanced head and neck cancer: 10-year follow-up of the UK Head and Neck (UKHAN1) trial. Lancet Oncol. 2010 Jan;11(1):66-74. doi: 10.1016/S1470-2045(09)70306-7. Epub 2009 Oct 29.