NCT00004227

Brief 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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at below P25 for phase_3 head-and-neck-cancer

Timeline
Completed

Started Apr 1999

Typical duration for phase_3 head-and-neck-cancer

Geographic Reach
1 country

3 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 1999

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

January 28, 2000

Completed
3 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2007

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2008

Completed
Last Updated

February 6, 2014

Status Verified

November 1, 2012

Enrollment Period

7.9 years

First QC Date

January 28, 2000

Last Update Submit

February 5, 2014

Conditions

Head and Neck Cancer

Keywords

stage III squamous cell carcinoma of the oropharynxstage IV squamous cell carcinoma of the oropharynxrecurrent squamous cell carcinoma of the oropharynxstage III squamous cell carcinoma of the hypopharynxstage IV squamous cell carcinoma of the hypopharynxrecurrent squamous cell carcinoma of the hypopharynxstage III squamous cell carcinoma of the larynxstage IV squamous cell carcinoma of the larynxrecurrent squamous cell carcinoma of the larynx

Study Arms (2)

Arm I

PLACEBO COMPARATOR

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.

Procedure: conventional surgeryRadiation: radiation therapy

Arm II

ACTIVE COMPARATOR

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.

Biological: cetuximabProcedure: conventional surgeryRadiation: radiation therapy

Interventions

cetuximabBIOLOGICAL
Arm II
conventional surgeryPROCEDURE
Arm IArm II
radiation therapyRADIATION
Arm IArm II

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (3)

Kimball Medical Center

Lakewood, New Jersey, 08701, United States

Location

Monmouth Medical Center

Long Branch, New Jersey, 07740-6395, United States

Location

ImClone Systems, Incorporated

Somerville, New Jersey, 08876, United States

Location

Related Publications (5)

  • 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 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. doi: 10.1016/S1470-2045(09)70311-0. Epub 2009 Nov 10.

    PMID: 19897418RESULT

  • 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 Engl J Med. 2006 Feb 9;354(6):567-78. doi: 10.1056/NEJMoa053422.

    PMID: 16467544RESULT

  • 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.

    RESULT

  • 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.

    RESULT

  • Bonner J, Giralt J, Harari P, Spencer S, Schulten J, Hossain A, Chang SC, Chin S, Baselga J. Cetuximab and Radiotherapy in Laryngeal Preservation for Cancers of the Larynx and Hypopharynx: A Secondary Analysis of a Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2016 Sep 1;142(9):842-9. doi: 10.1001/jamaoto.2016.1228.

    PMID: 27389475DERIVED

MeSH Terms

Conditions

Head and Neck NeoplasmsSquamous Cell Carcinoma of Head and Neck

Interventions

CetuximabRadiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsCarcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsTherapeutics

Study Officials

  • James A. Bonner, MD

    University of Alabama at Birmingham

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 28, 2000

First Posted

January 27, 2003

Study Start

April 1, 1999

Primary Completion

March 1, 2007

Study Completion

May 1, 2008

Last Updated

February 6, 2014

Record last verified: 2012-11

Locations

US(3)