Head and Neck CancerPhase 3NCT00004227
Radiation Therapy With or Without Cetuximab in Treating Patients With Stage III or Stage IV Cancer of the Oropharynx, Hypopharynx, or Larynx
A Phase 3 study testing cetuximab, conventional surgery and radiation therapy in people with Head and Neck Cancer, run by University of Alabama at Birmingham at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- cetuximab, conventional surgery and radiation therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 1999to May 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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 locations and contacts
3 sites in 1 country.
United States3 sites
Kimball Medical Center
Lakewood, New Jersey, 08701
Monmouth Medical Center
Long Branch, New Jersey, 07740-6395
ImClone Systems, Incorporated
Somerville, New Jersey, 08876
About this study
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
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.
Read the 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.
- Conditions
- Head and Neck Cancer
- Being tested
- cetuximab, conventional surgery, radiation therapy
- Keywords
- stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
conventional surgeryProcedure or surgery
radiation therapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: conventional surgery; Radiation: 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. Receives: Biological: cetuximab; Procedure: conventional surgery; Radiation: radiation therapy |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startApr 1999
- Primary completionMar 2007
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- James A. Bonner, MD, Study chair, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004227
- Sponsor's protocol ID
- CDR0000067468
- Other IDs
- UAB-9901, IMCL-CP02-9815, NCI-G99-1657
- Status last verified
- Nov 2012
- First submitted
- 28 Jan 2000
- Last updated
- 6 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19897418Bonner 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.
PubMed 16467544Bonner 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.
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.
PubMed 27389475
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00004227
- Acronym / sponsor ID
- CDR0000067468
- Conditions
- Head and Neck Cancer
- Keywords
- stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 1999
- Primary completion
- Mar 2007 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Placebo comparator | Procedure: conventional surgery, Radiation: radiation therapyPatients 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 | Active comparator | Biological: cetuximab, Procedure: conventional surgery, Radiation: radiation therapyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cetuximab | Biological | Arm II |
| conventional surgery | Procedure or surgery | Arm I, Arm II |
| radiation therapy | Radiation | Arm I, Arm II |
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2014.
- Results publication: PubMed 19897418Bonner 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.
- Results publication: PubMed 16467544Bonner 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.
- Results publicationBonner 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.
- Results publicationBonner 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.
- Derived from this study: PubMed 27389475Bonner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James A. Bonner, MD study chair
University of Alabama at Birmingham
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cetuximab, conventional surgery and radiation therapy in people with Head and Neck Cancer, run by University of Alabama at Birmingham at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00004227, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2014.