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

Alternate Title

Radiation Therapy With or Without Cetuximab in Treating Patients With Stage III or Stage IV Cancer of the Oropharynx, Hypopharynx, or Larynx

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over NCI, Pharmaceutical / Industry UAB-9901 IMCL-CP02-9815, NCI-G99-1657, NCT00004227

Objectives

1. Compare the rate of locoregional disease control maintained for 1 year in patients with advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx treated with radiotherapy with or without concurrent cetuximab.
2. Compare the response rates, progression-free survival and overall survival rates, and quality of life in patients treated with these regimens.
3. Compare acute and late toxicity of these regimens in these patients.
4. Determine tumor epidermal growth factor receptor levels in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically proven advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx
  • Stage III

    OR

  • Stage IV without distant metastases



• Measurable disease



• Tumor tissue available for immunohistochemical assay of epidermal growth factor receptor expression

Prior/Concurrent Therapy:

Biologic therapy:

• No prior cetuximab or other murine monoclonal antibody

Chemotherapy:

• At least 3 years since prior systemic chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to head and neck
• No other concurrent radiotherapy

Surgery:

• No prior surgery for indicator lesion except biopsy
• Study radiotherapy must not be a part of a postoperative regimen after primary surgical resection

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 1 year

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT and SGPT no greater than 2 times upper limit of normal

Renal:

• Creatinine no greater than 1.5 mg/dL

  OR

• Creatinine clearance at least 50 mL/min
• Calcium normal

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Medically able to withstand a course of definitive radiotherapy
• No medical or psychologic condition that would preclude informed consent or compliance
• No other malignancy within the past 3 years except basal cell skin cancer or preinvasive carcinoma of the cervix

Expected Enrollment

Approximately 416 patients (208 per arm) will be accrued for this study within approximately 5 years.

Outline

This is a randomized, multicenter study. Patients are stratified by Karnofsky performance status (60-80% vs 90-100%), nodal stage (N0 vs N+), tumor stage (T1-3 vs T4), and radiotherapy schedule (concurrent boost vs once daily vs twice daily).

Patients are randomized to 1 of 2 treatment arms:

• Arm I: Patients undergo radiotherapy beginning on day 1. Patients are assigned to 1 of 3 radiotherapy groups:
  • Group 1: Patients undergo concurrent boost radiotherapy comprised of radiotherapy once daily 5 days a week for 3.5 weeks followed by radiotherapy twice daily 5 days a week for 2.5 weeks.
  
  
  
  • Group 2: Patients undergo radiotherapy once daily 5 days a week for 7 weeks.
  
  
  
  • Group 3: Patients undergo radiotherapy twice daily 5 days a week for 6-6.5 weeks.
  
  
  



• Arm II: Patients receive a test dose of cetuximab IV over 10 minutes on day 1. Patients who do not experience grade 4 anaphylactic reaction receive a loading dose of cetuximab IV over 2 hours beginning 30 minutes after completion of test dose. Patients receive maintenance cetuximab IV over 1 hour on day 8. Maintenance cetuximab repeats every week for 7 courses. Beginning on day 8, patients undergo radiotherapy as in arm I concurrently with maintenance cetuximab. There must be an hour interval between the completion of cetuximab infusion and the start of any radiotherapy.

Patients with more than N1 neck disease at initial presentation undergo neck dissection 4-8 weeks after the completion of radiotherapy.

Quality of life is assessed before initiation of study therapy, at 8 weeks, and then every 4 months for 1 year.

Patients are followed at 8 weeks, every 4 months for 2 years, and then every 6 months for 3 years.

Bonner JA, Harari PM, Giralt J, et al.: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354 (6): 567-78, 2006.[PUBMED Abstract]

Bonner JA, Harari PM, Giralt J, et al.: The relationship of cetuximab-induced rash and survival in patients with head and neck cancer treated with radiotherapy and cetuximab. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-120, S73, 2005.

Bonner JA, Girald J, Harari PM, et al.: Phase III evaluation of radiation with and without cetuximab for locoregionally advanced head and neck cancer. [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-31, S147-8, 2004. Available online. Last accessed February 3, 2005.

Trial Contact Information

Trial Lead Organizations

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

James Bonner, MD, Protocol chair		Ph: 205-934-2756

Registry Information
Official Title		Randomized Phase III Trial to Compare Radiation Therapy Alone with Radiation Therapy and Concomitant Anti-EGFr Antibody (C225) for Locally Advanced Squamous Cell Carcinomas of the Head and Neck
Trial Start Date		2000-05-16
Registered in ClinicalTrials.gov		NCT00004227
Date Submitted to PDQ		1999-12-09
Information Last Verified		2001-11-01
NCI Grant/Contract Number		P30-CA13148