Completed

A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck

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What is being tested

cetuximab

+ cisplatin
+ radiation therapy
Biological
Drug
Radiation
Who is being recruted

Carcinoma
+3

+ Carcinoma, Squamous Cell
+ Neoplasms
Over 18 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: April 2004
See protocol details

Summary

Principal SponsorRadiation Therapy Oncology Group
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: April 1, 2004Actual date on which the first participant was enrolled.

OBJECTIVES: Primary * Compare disease-free survival of patients with resected stage III or IV squamous cell carcinoma or lymphoepithelioma of the head and neck treated with adjuvant cetuximab in combination with chemoradiotherapy comprising docetaxel vs cisplatin. Secondary * Compare the safety and efficacy of these regimens in these patients. * Compare locoregional control and overall survival rates in patients treated with these regimens. * Correlate epidermal growth factor receptor (total and phosphorylated), pMAPK, pAKT, Stat-3, Ki-67, cyclo-oxygenase-2, and cyclin B1 expression with outcome in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1), risk category (positive margins vs high risk \[i.e., ≥ 2 positive nodes or extracapsular nodal extension\]) and use of intensity-modulated radiotherapy (no vs yes). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive cetuximab IV over 2 hours on day 1 (week 1). Patients then receive cetuximab IV over 1 hour and cisplatin IV over 1 hour before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Patients undergo radiotherapy once daily, 5 days a week, beginning on day 8 for a total of 6 weeks (weeks 2-7). * Arm II: Patients receive cetuximab and undergo radiotherapy as in arm I. Patients also receive docetaxel IV over 30 minutes before radiotherapy on days 8, 15, 22, 29, 36, and 43 (weeks 2-7). Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 4 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within approximately 29 months.

Official TitleA Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck 
NCT00414674NCT00084318
Principal SponsorRadiation Therapy Oncology Group
Last updated: January 14, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
238 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

None (Single-arm trial)
: If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment
: Everyone gets the same treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled
: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Carcinoma
Carcinoma, Squamous Cell
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Criteria

DISEASE CHARACTERISTICS: * Histologically confirmed squamous cell carcinoma of the head and neck meeting the following criteria: * Site of tumor origin in the oral cavity, oropharynx, larynx, or hypopharynx (excluding lip, nasopharynx, or sinuses) * Gross total resection must be completed within 7 weeks of randomization, with pathology demonstrating one or more of the following risk factors: * Histologic extracapsular nodal extension * Histologic involvement of ≥ 2 regional lymph nodes * Invasive cancer seen on microscopic evaluation of the resection margin, with no evidence of gross tumor residual. * Tonsillar cancer patients who undergo transoral excision of all gross tumor are eligible provided extracapsular nodal extension or involvement of ≥ 2 regional lymph nodes is histologically confirmed * American Joint Committee on Cancer (AJCC) pathological stage III or IV * No evidence of distant metastases * No synchronous or concurrent head and neck primary tumors PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-1 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 2,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin \> 8.0 g/dL Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT), and alkaline phosphatase meeting 1 of the following parameters: * Alkaline phosphatase ≤ ULN AND AST or ALT ≤ 5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN * Alkaline phosphatase ≤ 5 times ULN AND AST or ALT ≤ ULN Renal * Creatinine ≤ 1.5 mg/dL Cardiovascular * No unstable angina * No uncontrolled hypertension * No myocardial infarction within the past 6 months (unless successfully treated with coronary artery bypass surgery or percutaneous transluminal coronary angioplasty) * No uncontrolled arrhythmia * No congestive heart failure * No more than 2 heart-related hospitalizations within the past year * No other active cardiac disease Pulmonary * No more than 2 hospitalizations for chronic obstructive pulmonary disease within the past year Neurologic * No pre-existing peripheral neuropathy ≥ grade 2 * No uncontrolled seizure disorder * No active neurological disease Other * No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 * No other invasive malignancy within the past 3 years except nonmelanoma skin cancer * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No prior anti-epidermal growth factor receptor antibody therapy Chemotherapy * More than 3 years since prior cytotoxic chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior head and neck radiotherapy Surgery * See Disease Characteristics Other * No prior tyrosine kinase inhibitor therapy


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Loading dose of cetuximab followed by radiation therapy with weekly cisplatin and cetuximab.

400 mg/m\^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m\^2 intravenously over 60 minutes in weeks 2 through 7.

30 mg/m\^2 intravenously infused over over 60 minutes in weeks 2 through 7.

60 Gy (2 Gy once a day, 5 times a week)
Group II
Experimental
Loading dose of cetuximab followed by radiation therapy (RT) with weekly docetaxel and cetuximab.

400 mg/m\^2 intravenously over 120 minutes on day 1 (week 1) followed by 250 mg/m\^2 intravenously over 60 minutes in weeks 2 through 7.

15 mg/m\^2 intravenously infused over 30 minutes in weeks 2 through 7.

60 Gy (2 Gy once a day, 5 times a week)
Study Objectives
Primary Objectives

Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise.
Secondary Objectives

Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored).

Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown.

Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was \>30%. \[RTOG = Radiation Therapy Oncology Group\]

Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment.

Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored).


Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 160 locations
Suspended
University of Alabama at Birmingham Comprehensive Cancer CenterBirmingham, United StatesSee the location
Suspended
Mobile Infirmary Medical CenterMobile, United States
Suspended
Arizona Oncology Services FoundationPhoenix, United States
Suspended
Virginia G. Piper Cancer Center at Scottsdale Healthcare - OsbornScottsdale, United States

Completed160 Study Centers
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