Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Adjuvant Cetuximab and Chemoradiotherapy Using Either Cisplatin or Docetaxel in Treating Patients With Resected Stage III or Stage IV Squamous Cell Carcinoma or Lymphoepithelioma of the Head and Neck

Basic Trial Information

Objectives

Primary

1. Compare disease-free survival of patients with resected stage III or IV squamous cell carcinoma or lymphoepithelioma of the head and neck treated with adjuvant cetuximab in combination with chemoradiotherapy comprising docetaxel vs cisplatin.

Secondary

1. Compare the safety and efficacy of these regimens in these patients.
2. Compare locoregional control and overall survival rates in patients treated with these regimens.
3. Correlate epidermal growth factor receptor (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, cyclo-oxygenase-2, and cyclin B1 expression with outcome in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed squamous cell carcinoma of the head and neck meeting the following criteria:
  • Site of tumor origin in the oral cavity, oropharynx, larynx, or hypopharynx (excluding lip, nasopharynx, or sinuses)
  • Gross total resection must be completed within 7 weeks of randomization, with pathology demonstrating one or more of the following risk factors:
    • Histologic extracapsular nodal extension
    • Histologic involvement of ≥ 2 regional lymph nodes
    • Invasive cancer seen on microscopic evaluation of the resection margin, with no evidence of gross tumor residual. or lymphoepithelioma of the oral cavity, oropharynx, larynx, or hypopharynx
    • Tonsillar cancer patients who undergo transoral excision of all gross tumor are eligible provided extracapsular nodal extension or involvement of ≥ 2 regional lymph nodes is histologically confirmed
  • Stage III or IV disease after gross total resection completed within the past 7 weeks

• No evidence of distant metastases

• No synchronous or concurrent head and neck primary tumors

Prior/Concurrent Therapy:

Biologic therapy

• No prior anti-epidermal growth factor receptor antibody therapy

Chemotherapy

• More than 3 years since prior cytotoxic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior head and neck radiotherapy
• No concurrent intensity-modulated radiotherapy

Surgery

• See Disease Characteristics

Other

• No prior tyrosine kinase inhibitor therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 2,000/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin > 8.0 g/dL

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST or ALT, and alkaline phosphatase meeting 1 of the following parameters:
  • Alkaline phosphatase ≤ ULN AND AST or ALT ≤ 5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
  • Alkaline phosphatase ≤ 5 times ULN AND AST or ALT ≤ ULN

Renal

• Creatinine ≤ 1.5 mg/dL

Cardiovascular

• No unstable angina
• No uncontrolled hypertension
• No myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass surgery or percutaneous transluminal coronary angioplasty)
• No uncontrolled arrhythmia
• No congestive heart failure
• No more than 2 heart-related hospitalizations within the past year
• No other active cardiac disease

Pulmonary

• No more than 2 hospitalizations for chronic obstructive pulmonary disease within the past year

Neurologic

• No pre-existing peripheral neuropathy ≥ grade 2
• No uncontrolled seizure disorder
• No active neurological disease

Other

• No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
• No other concurrent illness that would preclude study participation
• No concurrent psychiatric illness that would preclude study participation
• No other concurrent physical condition (e.g., infectious disease) that would preclude study participation
• No prisoners
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

Expected Enrollment

A total of 230 patients (115 per treatment arm) will be accrued for this study within approximately 29 months.

Outcomes

Disease-free survival
Treatment tolerance
Frequency of toxicity (grade 5 and acute non-hematologic grade 4)
Frequency of other acute and late toxicity
Overall survival
Local-regional control
Correlation of EGFR (total and phosphorylated) pMAPK, pAKT, Stat-3, KI-67, COX-2, and cyclin B1 expression with local-regional control, and overall and disease-free survival

Outline

This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1), risk category (positive margins vs high risk [i.e., ≥ 2 positive nodes or extracapsular nodal extension]) and use of intensity-modulated radiotherapy (no vs yes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cetuximab IV over 2 hours on day 1 (week 1). Patients then receive cetuximab IV over 1 hour and cisplatin IV over 1 hour before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Patients undergo radiotherapy once daily, 5 days a week, beginning on day 8 for a total of 6 weeks (weeks 2-7).

• Arm II: Patients receive cetuximab and undergo radiotherapy as in arm I. Patients also receive docetaxel IV over 30 minutes before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7).

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 4 years, and then annually thereafter.

Harari PM, Harris J, Kies MS, et al.: Phase II randomized trial of surgery followed by chemoradiation plus cetuximab for high-risk squamous cell carcinoma of the head and neck (RTOG 0234). [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-22, S13, 2007.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Paul Harari, MD, Protocol chair		Ph: 608-263-8500; 800-622-8922
Merrill Kies, MD, Protocol co-chair		Ph: 713-792-6363; 800-392-1611 Email: mkies@mdanderson.org
Jeffrey Myers, MD, PhD, FACS, Protocol co-chair		Ph: 713-745-2667; 800-392-1611 Email: jmyers@mdanderson.org

Registry Information
Official Title		A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck
Trial Start Date		2004-04-20
Registered in ClinicalTrials.gov		NCT00084318
Date Submitted to PDQ		2004-03-03
Information Last Verified		2006-12-01
NCI Grant/Contract Number		CA21661

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