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

Alternate Title

Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	RTOG-0522 RTOG 0522, NCT00265941

Special Category: NCI Web site featured trial, CTSU trial, NCI - CMS pilot project trial

Objectives

Primary

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

Secondary

1. 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.
2. Correlate the expression of EGFR and its down-stream molecules with outcome in patients participating in this component of the trial.
3. Correlate pre-treatment PET scan findings with disease-free survival, overall survival, and local-regional control in patients participating in this component of the trial.
4. Correlate post-treatment PET scan findings with nodal response and nodal relapse in patients participating in this component of the trial.

Entry Criteria

Disease Characteristics:

• Histologically proven (from primary lesion and/or lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx
  • Stage III or IV disease (T2, N2-3, M0; T3-4, any N, M0)
    • No distant metastases
  • The following primary tumor sites are excluded:
    • Oral cavity
    • Nasopharynx
    • Sinuses
    • Salivary glands

Prior/Concurrent Therapy:

• No prior systemic chemotherapy for the study cancer
  • Prior chemotherapy for a different cancer is allowed
• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• No initial surgical treatment (excluding diagnostic biopsy of the primary site or nodal sampling of neck disease)
• No radical or modified neck dissection
• No prior therapy that specifically and directly targets the EGFR pathway
• Patients participating in RTOG-0522 are also eligible for and are strongly encouraged to participate in RTOG-0514, the Head and Neck tissue banking protocol

Patient Characteristics:

• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) ≥ 1,800/mm³
• Platelets ≥ 100,000/mm³
• Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable)
• Bilirubin ≤ 1.5 mg/dL (Gilbert’s disease as the sole cause of elevated bilirubin may be allowed at the discretion of the principal investigator)
• AST or ALT ≤ 2 times the upper limit of normal
• Serum creatinine ≤ 1.5 mg/dL
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment)
• No prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
• No unstable angina and/or congestive heart failure requiring hospitalization in past 6 months
• Left ventricular ejection fraction ≥ 45%
• No transmural myocardial infarction within the last 6 months
• No acute bacterial or fungal infection requiring intravenous antibiotics
• No chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
• No acquired immune deficiency syndrome (AIDS)
  • HIV testing is not required for entry into this protocol
  • Protocol-specific requirements may also exclude immuno-compromised patients
• No prior allergic reaction to the study drug(s)
• No other uncontrolled condition, which in the opinion of the investigator, would interfere in the safe and timely completion of study procedures
• No comorbidity of uncontrolled diabetes (i.e., symptomatic hyperglycemia)
• No other severe active comorbidity

Expected Enrollment

Approximately 720 patients will be accrued for this study.

Outcomes

Disease-free survival (DFS)

Overall survival (OS)
Local-regional control (LRC)
Mucositis toxicity ≥ grade 3
Other toxicity ≥ grade 3
Protocol treatment delivery
Death ≤ 30 days after discontinuation of protocol treatment
Quality of life as measured by Performance Status Scale for Head and Neck Cancer and the European Quality of Life questionnaire (EQ-5D)
Quality of life as measured by Functional Assessment of Cancer Therapy-General version
Correlation of expression of epidermal growth factor receptor or its down-stream molecules (e.g., MAPK, AKT, Stat-3, PKC) with DFS, OS, and LRC
Correlation of pre-treatment positron emission tomography (PET)/CT scan findings with DFS, OS, and LRC
Correlation of post-treatment PET/CT scan findings with pathologic nodal complete response and nodal relapse rate at 2 years in clinical N2-3 patients

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.

• Arm I: Patients undergo either 3D-conformal radiotherapy or IMRT once or twice a day, 5 or 6 days a week, for 6 weeks. Patients also receive cisplatin IV over 1 hour on days 1 and 22 (weeks 1 and 4) during radiotherapy.
• Arm II: Patients receive cetuximab IV over 1-2 hours once in weeks 0-7. Beginning in week 1, patients also undergo radiotherapy and receive cisplatin as in arm I.

In both arms, patients with persistent nodal disease (any stage) (i.e., a residual palpable or radiographic abnormality) undergo neck dissection* approximately 9-10 weeks after completion of treatment.

 [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.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

K. Kian Ang, MD, PhD, Principal investigator		Ph: 713-563-2300; 800-392-1611

Related Information

Featured trial article

Registry Information
Official Title		A Randomized Phase III Trial of Concurrent Accelerated Radiation and Cisplatin Versus Concurrent Accelerated Radiation, Cisplatin, and Cetuximab (C225) [Followed by Surgery for Selected Patients] for Stage III and IV Head and Neck Carcinomas
Trial Start Date		2005-11-22
Trial Completion Date		2014-06-01 (estimated)
Registered in ClinicalTrials.gov		NCT00265941
Date Submitted to PDQ		2005-11-15
Information Last Verified		2009-09-09
NCI Grant/Contract Number		CA21661

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