Clinical trial NCT00265941
Conditions: Head and Neck Cancer
Keywords: stage III squamous cell carcinoma of the hypopharynx stage IV squamous cell carcinoma of the hypopharynx stage III squamous cell carcinoma of the larynx stage IV squamous cell carcinoma of the larynx stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx
Sponsor: Radiation Therapy Oncology Group
Start date: 2005-11-01; Completion date: 2022-05-20
Enrollment: 940 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving radiation therapy and cisplatin together with cetuximab may kill more tumor cells. It is not yet known whether radiation therapy and cisplatin are more effective with or without cetuximab in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy, cisplatin, and cetuximab to see how well they work compared to radiation therapy and cisplatin in treating patients with stage III or stage IV head and neck cancer.

Detailed description:
OBJECTIVES:

Primary

* Evaluate whether the addition of cetuximab to a concurrent radiation-cisplatin regimen will improve progression-free survival in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx.

Secondary

* Determine the impact of the addition of cetuximab to a concurrent radiation-cisplatin regimen on overall survival, local-regional control, acute and late toxic effects, quality of life, and health utilities in these patients.
* Correlate the expression of epidermal growth factor receptor (EGFR) and its down-stream molecules with outcome in patients participating in this component of the trial.
* Correlate pre-treatment positron emission tomography (PET) scan findings with progression-free survival, overall survival, and local-regional control in patients participating in this component of the trial.
* Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to primary site (larynx vs non-larynx), nodal stage (N0 vs N1, N2a, N2b vs N2c, N3), Zubrod performance status (0 vs 1), use of intensity modulated radiotherapy (IMRT) (no vs yes), and pre-treatment PET/CT scan (no vs yes). Patients are randomized to 1 of 2 treatment arms.

NOTE: \*A neck dissection is optional for patients with multiple lymph nodes or lymph nodes \> 3 cm in diameter who achieve a complete clinical and radiographic response in the neck.

Quality of life is assessed at baseline, once during the last 2 weeks of treatment, at 3 and 12 months from the start of treatment, and then annually for 4 years.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

Arms: arm 1: Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin arm 2: Radiation therapy (RT) as accelerated fractionation by concomitant boost (AFX-CB) or intensity-modulated radiation therapy (IMRT) plus cisplatin plus cetuximab
Interventions: intervention 1: cetuximab intervention 2: cisplatin intervention 3: Accelerated Fractionation by Concomitant Boost intervention 4: Intensity-modulated radiation therapy
Intervention descriptions: intervention 1: Cetuximab 400 mg/m\^2 IV loading dose 5-7 days before start of radiation therapy, then 250 mg/m\^2 IV weekly for 7 weeks intervention 2: Cisplatin 100 mg/m\^2 IV on days 1 and 22 intervention 3: 3DCRT 54 Gy in 30 1.8 Gy fractions over 6 weeks with boost 18 Gy in 12 1.5 Gy fractions for last 12 days, for a total of 72 Gy in 42 fractions over 6 weeks intervention 4: 70 Gy in 35 2.0 Gy fractions over 6 weeks with 6 fractions per week (on Saturday or as second daily fraction) in 5 of the 6 weeks.

Protocol documents: