Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

OBJECTIVES:

Primary

• 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

• 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 EGFR and its down-stream molecules with outcome in patients participating in this component of the trial.

• 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.

• 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.

• 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.

PROJECTED ACCRUAL: Approximately 720 patients will be accrued for this study.

Eligibility 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

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1

• Absolute neutrophil count (ANC) ≥ 1,800/mm^3

• Platelets ≥ 100,000/mm^3

• 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

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Radiation Therapy Oncology Group

K. Kian Ang

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00265941
Information obtained from ClinicalTrials.gov on November 20, 2012

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