RT With or Without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck Cancer

Phase 3

Active, not recruiting

Conditions: Head and Neck Cancer

Interventions: Radiation: intensity-modulated radiation therapy
Biological: cetuximab

Registration Number: NCT00956007

Lead Sponsor: Radiation Therapy Oncology Group

Brief Summary: RATIONALE: Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether radiation therapy is more effective when given alone or together with cetuximab in treating patients with head and neck cancer that has been removed by surgery.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with cetuximab in treating patients who have undergone surgery for locally advanced head and neck cancer.

Detailed Description: OBJECTIVES:

Primary

* Determine whether the addition of cetuximab to postoperative intensity-modulated radiotherapy (IMRT) will improve overall survival (OS) in patients with locally advanced squamous cell carcinoma of the head and neck at intermediate risk following surgery.

Secondary

* Assess the impact of the addition of cetuximab to postoperative IMRT on disease-free survival (DFS) of these patients.

* Assess the impact of the addition of cetuximab to postoperative IMRT on acute and late dysphagia, xerostomia, skin toxicity, and other toxicities according to common Toxicity Criteria for Adverse Effects (CTCAE), v. 4 and their relationships with patient-reported outcomes at 3, 12, and 24 months.

* Analyze tumor for epidermal growth factor receptor (EGFR), specifically the extent of EGFR overexpression by immuno-histochemistry (IHC) and Fluorescence in situ hybridization (FISH) analysis, EGFRvIII expression, as well as the association of these assay data with OS and DFS.

* Analyze tumor for human papillomavirus (HPV) infection (as defined by in situ hybridization), specifically, within the cohort of patients with oropharynx cancer, to perform an exploratory analysis of the impact of HPV on DFS and OS of this patient subset.

* Analyze tumor DNA for TP53 mutations as a predictor of response to cetuximab and prognosis.

* Analyze germline DNA of polymorphic variants in EGFR intron repeats as a predictor of response to cetuximab.

Tertiary

* Assess the impact of the addition of cetuximab to postoperative IMRT on loco-regional control.

* Assess the impact of the addition of cetuximab to postoperative IMRT on patient-reported quality of life, swallowing, xerostomia, and skin toxicity based on head and neck specific instruments, including the Performance Status Scale for Head and Neck Cancer (PSS-HN), the Functional Assessment of Cancer Therapy-Head \& Neck (FACT-H\&N), the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS), and the Dermatology Life Quality Index (DLQI).

* Assess the impact of the addition of cetuximab to postoperative IMRT on cost-utility analysis using the EuroQol (EQ-5D).

* Evaluate the utility of image-guided radiotherapy (IGRT) as a means of enhancing the efficacy (i.e., loco-regional control) of IMRT while reducing the acute and/or late toxicity (particularly xerostomia) and improving patient-reported outcomes (particularly XeQOLS scores).

* Retrospectively compare the loco-regional control rate in patients treated with IMRT alone (no IGRT or cetuximab) with similar patients treated with external beam radiotherapy alone in the postoperative clinical trial Radiation Therapy Oncology Group (RTOG)-95 01.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage (T1-3 vs T4a), EGFR expression (high \[≥ 80% of cells staining positive\] vs low \[\< 80% of cells staining positive\] vs not evaluable), primary site of disease (oral cavity vs larynx vs oropharynx p16+ vs oropharynx p16- vs oropharynx, p16 not evaluable), and use of image-guided radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2 hours once weekly beginning at least 5 days prior to the start of IMRT and continuing for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and at 3, 12, and 24 months.

Tissue samples are collected periodically for further laboratory analysis.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 702

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I: Intensity-Modulated Radiotherapy	intensity-modulated radiation therapy	Radiation therapy: 60 Gy intensity-modulated radiotherapy (IMRT), 2 Gy/day in 30 fractions (5 days a week for 6 weeks).
Arm II: IMRT plus cetuximab	cetuximab	Radiation therapy (RT): 60 Gy IMRT, 2 Gy/day in 30 fractions (5 days a week for 6 weeks). Cetuximab: 400 mg/m\^2 intravenously (IV) at least 5 days prior to IMRT; 250 mg/m\^2 IV once a week for 6 weeks during RT and continuing 4 weeks after RT.
Arm II: IMRT plus cetuximab	intensity-modulated radiation therapy	Radiation therapy (RT): 60 Gy IMRT, 2 Gy/day in 30 fractions (5 days a week for 6 weeks). Cetuximab: 400 mg/m\^2 intravenously (IV) at least 5 days prior to IMRT; 250 mg/m\^2 IV once a week for 6 weeks during RT and continuing 4 weeks after RT.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Alive (Overall Survival)	From randomization to date of death or last follow-up. Maximum follow-up at time of analysis was 12.1 years.	Overall survival time is defined as time from registration/randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. Analysis occurred after all participants had potentially been on study for at least 5 years. The distributions of survival times are compared, which is reported in the statistical analysis results. Five-year rates are provided.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Other ≥ Grade 3 Adverse Events Related to Protocol Treatment	From start of radiation therapy to 90 days.	Adverse events other than dysphagia, dermatitis radiation, and rash acneiform. Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment were included. If relationship was missing, it was assumed to be definitely, probably, or possibly related to protocol treatment. Acute adverse events are those occurring within 90 days of the start of radiation therapy.
Percentage of Participants With Other ≥ Grade 3 Late Adverse Events Related to Protocol Treatment	From 91 days after start of radiation therapy to date of last reported follow-up. Maximum follow-up at time of analysis was 12.1 years.	Adverse events other than dysphagia, dermatitis radiation, and rash acneiform. Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment were included. If relationship was missing, it was assumed to be definitely, probably, or possibly related to protocol treatment. Late adverse events are those occurring after days from the start of radiation therapy.
Percentage of Participants With ≥ Grade 3 Acute Dysphagia, Dry Mouth, or Skin Toxicity Related to Protocol Treatment	From start of radiation therapy to 90 days	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment were included. If relationship was missing, it was assumed to be definitely, probably, or possibly related to protocol treatment. Acute adverse events are those occurring within 90 days of the start of radiation therapy.
Disease-free Survival	From randomization to date of LRR, DM, death or last known follow-up, whichever occurred first. Maximum follow-up at time of analysis was 12.1 years.	Disease is defined as local-regional progression/recurrence (LRR) or distant metastasis (DM). LRR is defined as recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; both imaging and biopsy confirmation are strongly recommended. DM is defined as clear evidence of distant metastases; biopsy is recommended where possible. Disease-free survival time is defined as time from randomization to the date of first disease, death, or last known follow-up (censored), whichever occurred first. Disease-free survival rates are estimated using the Kaplan-Meier method. Analysis occurred after all participants had potentially been on study for at least 5 years. The distributions of disease-free survival times are compared, which is reported in the statistical analysis results. Five-year rates are provided.
Percentage of Participants With ≥ Grade 3 Late Dysphagia, Dry Mouth, or Skin Toxicity Related to Protocol Treatment	From 91 days after start of radiation therapy to date of last reported follow-up. Maximum follow-up at time of analysis was 12.1 years.	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events assessed to be definitely, probably, or possibly related to protocol treatment were included. If relationship was missing, it was assumed to be definitely, probably, or possibly related to protocol treatment. Late adverse events are those occurring after days from the start of radiation therapy.

Trial Locations

Locations (263): University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Arizona Oncology Associates-West Orange Grove
🇺🇸
Tucson, Arizona, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸
Auburn, California, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸
Cameron Park, California, United States
Mercy San Juan Medical Center
🇺🇸
Carmichael, California, United States
City of Hope
🇺🇸
Duarte, California, United States
UC San Diego Moores Cancer Center
🇺🇸
La Jolla, California, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸
Los Angeles, California, United States
Los Angeles County-USC Medical Center
🇺🇸
Los Angeles, California, United States
University of Southern California/Norris Cancer Center
🇺🇸
Los Angeles, California, United States
Scroll for more (253 remaining)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States