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

February 5, 2014 updated by: University of Alabama at Birmingham

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

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.

Study Overview

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New Jersey
      • Lakewood, New Jersey, United States, 08701
        • Kimball Medical Center
      • Long Branch, New Jersey, United States, 07740-6395
        • Monmouth Medical Center
      • Somerville, New Jersey, United States, 08876
        • ImClone Systems, Incorporated

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 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.
Active Comparator: 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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: James A. Bonner, MD, University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 1999

Primary Completion (Actual)

March 1, 2007

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

January 28, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

February 6, 2014

Last Update Submitted That Met QC Criteria

February 5, 2014

Last Verified

November 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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