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

The University of Alabama at Birmingham

Status and phase: Terminated; Phase 3

Conditions: Head and Neck Cancer

Treatments: Biological: cetuximab; Procedure: conventional surgery; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00004227

NCI-G99-1657

CDR0000067468

UAB-9901

IMCL-CP02-9815

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known if radiation therapy is more effective with or without cetuximab for cancer of the oropharynx, hypopharynx, or larynx.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without cetuximab in treating patients who have stage III or stage IV cancer of the oropharynx, hypopharynx, or larynx.

Full description

OBJECTIVES:

• 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.
• Compare the response rates, progression-free survival and overall survival rates, and quality of life in patients treated with these regimens.
• Compare acute and late toxicity of these regimens in these patients.
• Determine tumor epidermal growth factor receptor levels in patients treated with these regimens.

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.

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

Enrollment: 32 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

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/mm^3
• Platelet count at least 100,000/mm^3

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 2 patient groups, including a placebo group

Arm I

Placebo Comparator group

Description:

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.

Treatment:

Radiation: radiation therapy

Procedure: conventional surgery

Arm II

Active Comparator group

Description:

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. Radiotherapy groups remain the same as in Arm I: * 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.

Treatment:

Biological: cetuximab

Radiation: radiation therapy

Procedure: conventional surgery