Clinical trial NCT00089297
Conditions: Head and Neck Cancer
Keywords: Stage III head and neck cancer Stage IV head and neck cancer Cetuximab Paclitaxel Carboplatin
Sponsor: Eastern Cooperative Oncology Group
Start date: 2005-01-06; Completion date: 2011-02-01
Enrollment: 74 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: 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. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving cetuximab with combination chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving cetuximab after surgery may kill any tumor cells that remain.

PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy and radiation therapy works in treating patients who are undergoing surgery for stage III or stage IV head and neck cancer.

Detailed description:
OBJECTIVES:

Primary

* Determine the effect of induction therapy comprising cetuximab, paclitaxel, and carboplatin followed by chemoradiotherapy comprising cetuximab, paclitaxel, carboplatin, and radiotherapy and maintenance therapy comprising cetuximab on 1-year event-free survival (freedom from surgery at the primary site and freedom from recurrence and death) in patients with stage III or IV operable squamous cell cancer of the head and neck.

Secondary

* Determine the pathologic antitumor response at the primary site in patients treated with this regimen.
* Determine disease-free and overall survival of patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.
* Determine local/regional and distant failure rates in patients treated with this regimen.
* Determine the effect of this treatment regimen on selective biologic pathways, total and phosphorylated epidermal growth factor receptor, ERK/MAPK, and P13K/AKT in these patients.

OUTLINE: This is a multicenter study.

* Induction therapy (weeks 1-6): Patients receive cetuximab IV over 1-2 hours, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, and 36.

During week 7 or 8, patients undergo biopsy and evaluation of the primary site. Patients then proceed to chemoradiotherapy.

* Chemoradiotherapy (weeks 9-13): Patients receive cetuximab IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 15 minutes on days 57, 64, 71, 78, and 85. Patients also undergo radiotherapy once daily, 5 days a week, on weeks 9-13.

Patients with a positive biopsy at week 7 or 8 or persistent tumor at the primary site after induction therapy undergo a second biopsy after chemoradiotherapy at week 14. Patients with a negative biopsy at week 7 or 8 who achieve a complete clinical and pathological response at the primary site OR patients whose biopsy becomes negative at week 14 receive an additional 3-weeks of chemoradiotherapy beginning at week 15. Patients receive cetuximab, carboplatin, and paclitaxel as in chemoradiotherapy (as outlined above) on days 99, 106, and 113. Patients also undergo radiotherapy once daily, 5 days a week, for 3 weeks (weeks 15-17). Patients with N1-N3 disease undergo neck dissection in weeks 20-21.

Patients with a positive biopsy at week 14 do not receive additional chemoradiotherapy, but rather undergo surgical resection of the primary site in weeks 18-19. Patients with N1-N3 disease also undergo neck dissection at this time.

* Maintenance therapy: Beginning after completion of surgery and/or chemoradiotherapy, patients receive cetuximab IV over 1 hour once weekly for 6 months in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

ACTUAL ACCRUAL: A total of 74 patients were accrued for this study.

Arms: arm 1: Induction: Cetuximab (C225) 400 mg/m2 at wk 1 then 250 mg/m2 for 5 weeks. Paclitaxel (P) 90 mg/m2 IV and carboplatin (C) AUC = 2 IV were given weekly.

Restaging biopsy of primary site scheduled at wk 7. Concurrent chemoradiation: Radiation therapy at 200cGy/d/5 wks for a total of 50Gy and C225 at 250 mg/m2/wk. P following C225 at 30 mg/m2/wk and C following P at AUC = 1/week. Patients with a negative biopsy continued concurrent therapy to complete radiation (68-72Gy).

Restaging biopsy of primary site: Patients with positive biopsy at wk 7 or patients without a clinical complete response at the primary site after induction therapy had re-biopsy at wk 14. If the biopsy was negative, the patients continued concurrent therapy to complete radiation (68-72 Gy). If positive, resection of the primary site was done.

Additional concurrent chemoradiation: C225 at 250mg/m2/wk IV followed by P 30mg/m2/wk IV followed by C AUC = 1/wk and RT for 3 wks.
Interventions: intervention 1: Cetuximab intervention 2: Carboplatin intervention 3: Paclitaxel intervention 4: Radiation therapy
Intervention descriptions: intervention 1: Induction: An initial dose of cetuximab (C225) 400 mg/m2 (over 2 hours) was given week 1 only. Then, C225 was administered at dose of 250 mg/m2 (over 1 hour) weekly for 5 weeks.

Concurrent Chemoradiation (Weeks 9-13): C225 was administered at 250 mg/m2/wk (over 1 hour).

Restaging Biopsy of Primary Site (Week 14): Patients with positive biopsy of the primary site at week 7 or patients without a clinical complete response at the primary site after induction therapy were scheduled for re-biopsy of the primary site at week 14 after concurrent therapy (50 Gy). If the biopsy were negative after concurrent therapy, the patients were scheduled to continue concurrent therapy to complete radiation (68-72 Gy).

Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks. intervention 2: Induction Therapy (Week 1-6): The induction chemotherapy starting at week 1 included paclitaxel 90 mg/m2 IV over 1 hour weekly and carboplatin AUC = 2 IV over 30 minutes weekly. The paclitaxel and carboplatin doses were given on the same day, 1 hour after C225 dose was administered. For paclitaxel and carboplatin therapy, rounding of doses (to next decimal if above 0.5 and to lower decimal if below 0.5) was permitted.

Concurrent Chemoradiation (Weeks 9-13): Concurrent chemotherapy was consisted of paclitaxel following cetuximab at 30 mg/m2/wk (over 1 hour) and carboplatin following paclitaxel at AUC = 1/week (over 15 minutes).

Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks. intervention 3: Induction Therapy (Week 1-6): The induction chemotherapy starting at week 1 included paclitaxel 90 mg/m2 IV over 1 hour weekly and carboplatin AUC = 2 IV over 30 minutes weekly. The paclitaxel and carboplatin doses were given on the same day, 1 hour after C225 dose was administered. For paclitaxel and carboplatin therapy, rounding of doses (to next decimal if above 0.5 and to lower decimal if below 0.5) was permitted.

Concurrent Chemoradiation (Weeks 9-13): Concurrent chemotherapy was consisted of paclitaxel following cetuximab at 30 mg/m2/wk (over 1 hour) and carboplatin following paclitaxel at AUC = 1/week (over 15 minutes).

Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks. intervention 4: Concurrent Chemoradiation (Weeks 9-13): Radiation was given at 200cGy/d/5 weeks for a total dose of 50Gy (5000 cGy). Patients with a negative initial biopsy at week 7 were scheduled to continue concurrent therapy to complete radiation (68-72Gy).

If the biopsy was negative after concurrent therapy, the patients were scheduled to continue concurrent therapy to complete radiation (68-72 Gy).

Additional Concurrent Chemoradiation (weeks 15, 16 and 17): Concurrent therapy was consisted of C225 at 250mg/m2/week IV over 1 hour followed by paclitaxel 30mg/m2/week IV over 1 hour followed by carboplatin AUC = 1/week over 15 minutes and RT for three weeks.

Protocol documents: