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

Official Title

A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer

Summary:

RATIONALE: Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumour to help focus thin beams of radiation directly on the tumour, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumour cells and have fewer side effects. Monoclonal antibodies, such as cetuximab, can block tumour growth in different ways. Some block the ability of tumour cells to grow and spread. Others find tumour cells and help kill them or carry tumour-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.

Trial Description

Primary Outcome:

  • Overall survival
Secondary Outcome:
  • Adverse events (dysphagia, xerostomia, and skin toxicity) according to CTCAE, v. 4 and their relationships with patient-reported outcomes at 3, 12, and 24 months
  • Other acute adverse events (≤ 90 days from start of radiation therapy [RT]) according to CTCAE, v. 4
  • Other late adverse events (> 90 days from start of RT) according to CTCAE, v. 4
  • Disease-free survival
  • Loco-regional control
  • Quality of life as measured by Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) and EuroQol (EQ-5D) at baseline and at 3, 12, and 24 months
  • Xerostomia as measured by University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) at baseline and at 3, 12, and 24 months
  • Swallowing as measured by the normalcy of diet subscale of the Performance Status Scale for Head and Neck Cancer (PSS-HN) at baseline and at 3, 12, and 24 months
  • Skin toxicity as measured by the Dermatology Life Quality Index (DLQI) at baseline and at 3, 12, and 24 months
OBJECTIVES:
Primary
  • Determine whether the addition of cetuximab to postoperative intensity-modulated radiation therapy (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 tumour for epidermal growth factor receptor (EGFR), specifically the extent of EGFR overexpression by immuno-histochemistry (IHC) and FISH analysis, EGFRvIII expression, as well as the association of these assay data with OS and DFS.
  • Analyze tumour 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 tumour 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 radiation therapy (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 radiation therapy alone in the postoperative clinical trial Radiation Therapy Oncology Group (RTOG)-95 01.
OUTLINE:

This is a multicentre study. Patients are stratified according to clinical stage (T2-3 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 radiation therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.
  • Arm I: Patients undergo intensity-modulated radiation therapy (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.

View this trial on ClinicalTrials.gov

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