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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00004227
• Other study ID #: CDR0000067468
• Secondary ID: UAB-9901IMCL-CP0
• Status: Terminated
• Phase: Phase 3
• First received: January 28, 2000
• Last updated: February 5, 2014
• Start date: April 1999
• Est. completion date: May 2008

Study information

• Verified date: November 2012
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 32
• Est. completion date: May 2008
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• cetuximab

Procedure:
• conventional surgery

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Kimball Medical Center	Lakewood	New Jersey
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	ImClone Systems, Incorporated	Somerville	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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 acces

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Eng — View Citation

Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 random — View Citation

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.