Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Projected Accrual
Outline
Trial Contact Information

Alternate Title

Cetuximab, Combination Chemotherapy, and Radiation Therapy in Treating Patients Who Are Undergoing Surgery for Stage III or Stage IV Head and Neck Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Approved-not yet active 18 to 80 NCI ECOG-E2303

Objectives

Primary

1. Determine the effect of induction therapy comprising cetuximab, paclitaxel, and carboplatin followed by chemoradiotherapy comprising cetuximab, paclitaxel, carboplatin, and radiotherapy 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

1. Determine the pathologic antitumor response at the primary site in patients treated with this regimen.
2. Determine disease-free and overall survival of patients treated with this regimen.
3. Determine the toxicity of this regimen in these patients.
4. Determine local/regional and distant failure rates in patients treated with this regimen.
5. 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.
6. Determine the quality of life of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed squamous cell cancer of the head and neck
  • Biopsy confirmed at the primary site
  • Stage III or IV (T2-4, N1-N3)
  • No nasopharyngeal cancer



• Potentially operable with a high likelihood of achieving R0 resection
  • No fixed nodal metastasis to the spine or carotid artery
  • No invasion of the root of the tongue, pharyngeal muscle, post pharynx, or vertebral fascia
  • No invasion of laryngeal cartilage into strap muscles or tracheal invasion > 1 cm



• Measurable disease
  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR > 10 mm by spiral CT scan
  • Patients with clinically palpable cervical lymph nodes must be evaluated by CT scan and confirmed with fine needle aspiration
  • Patients with non-palpable neck nodes must be evaluated by CT scan
    • Radiographic findings are acceptable in the absence of clinically palpable lymph nodes

Prior/Concurrent Therapy:

Biologic therapy

• No prior immunotherapy for head and neck cancer
• No prior chimerized or murine monoclonal antibody therapy
• No prior anti-epidermal growth factor receptor (EGFR) antibody therapy

Chemotherapy

• No prior chemotherapy for head and neck cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for head and neck cancer
• No concurrent cobolt-60

Surgery

• No prior surgery for head and neck cancer

Other

• No prior tyrosine kinase inhibitor therapy, including inhibitors targeting EGFR pathways

Patient Characteristics:

Age

• 18 to 80

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin ≤ 1.5 mg/dL

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No significant history of cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure
• No uncontrolled arrhythmias

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known allergy to murine proteins or Cremophor EL
• No other malignancy within the past 5 years except lobular carcinoma in situ of the breast, carcinoma in situ of the cervix, basal cell cancer, or excised and controlled cutaneous squamous cell cancer (< 200 mm thick)

Projected Accrual

A total of 72 patients will be accrued for this study within 2.2 years.

Outline

This is a multicenter study.

• Induction therapy (weeks 1-6): Patients receive cetuximab IV over 1-2 hours, paclitaxel IV over 3 hours, 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 negative biopsy at week 7 or 8 and who achieve a complete clinical and pathological response at the primary site after induction therapy receive additional chemoradiotherapy beginning at week 14. Patients receive cetuximab, carboplatin, and paclitaxel as in chemoradiotherapy (as outlined above) on days 92, 99, and 106 (weeks 14-16). Patients also undergo radiotherapy once daily, 5 days a week, on weeks 15 and 16. Patients with N1-N3 disease undergo neck dissection on weeks 20-21.

Patients with a positive biopsy at week 7 or 8 or persistent tumor at the primary site after induction therapy undergo a second biopsy on week 14. Patients with a negative biopsy at week 14 receive additional chemoradiotherapy (as outlined above) on weeks 14-16. Patients with N1-N3 disease undergo neck dissection on 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 on weeks 18-19. Patients with N1-N3 disease also undergo neck dissection at this time.

Quality of life is assessed at baseline, at weeks 7 or 8, 14, and 20 during study treatment, and then at 3, 6, and 12 months after completion of study treatment.

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

Disclaimer

The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Harold Wanebo, MD, Protocol chair		Ph: 401-456-2464 Email: haroldjwanebo@juno.com
Barbara Burtness, MD, Protocol co-chair		Ph: 203-785-4110 Email: barbara.burtness@yale.edu

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