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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Radiation Therapy Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00956007
First received: August 8, 2009
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Biological: cetuximab
Radiation: intensity-modulated radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after 372 events have been reported. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: From start of treatment to 2 years after end of treatment. ] [ Designated as safety issue: Yes ]
  • Other acute adverse events (≤ 90 days from start of radiotherapy [RT]) according to CTCAE, v. 4 [ Time Frame: From start of treatment to 90 days. ] [ Designated as safety issue: Yes ]
  • Other late adverse events (> 90 days from start of RT) according to CTCAE, v. 4 [ Time Frame: From 90 days after start of treatment to last follow-up. ] [ Designated as safety issue: Yes ]
  • Disease-free survival [ Time Frame: From randomization to date of failure (local, regional or distant progression or death) or last follow-up. Analysis occurs at the same time as the primary outcome. ] [ Designated as safety issue: No ]
  • Loco-regional control [ Time Frame: From randomization to date of failure (local or regional progression or distant progression or death) or last follow-up. Analysis occurs at the same time as the primary outcome. ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: From randomization to 2 years. ] [ Designated as safety issue: No ]
  • Xerostomia as measured by University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) at baseline and at 3, 12, and 24 months [ Time Frame: From randomization to 2 years. ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: From randomization to 2 years. ] [ Designated as safety issue: No ]
  • Skin toxicity as measured by the Dermatology Life Quality Index (DLQI) at baseline and at 3, 12, and 24 months [ Time Frame: From randomization to 2 years. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 700
Study Start Date: November 2009
Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I: Intensity-Modulated Radiotherapy
Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
Radiation: intensity-modulated radiation therapy
Patients undergo radiotherapy.
Experimental: Arm II: IMRT plus cetuximab
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.
Biological: cetuximab
Given IV
Radiation: intensity-modulated radiation therapy
Patients undergo radiotherapy.

  Hide Detailed Description

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 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 (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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed squamous cell carcinoma (including variants, such as verrucous carcinoma, spindle cell carcinoma, or carcinoma not otherwise specified) of the head and neck, including the following subtypes:

    • Oral cavity
    • Oropharynx
    • Larynx
  • Clinical stage T1, N1-2, M0 OR T2-4a, N0-2, M0 disease based on the following diagnostic workup within the past 8 weeks:

    • General history and physical examination by a Radiation Oncologist and/or Medical Oncologist
    • Chest x-ray or chest CT scan (with or without contrast) or chest CT/PET scan (with or without contrast)
  • Must have undergone gross total resection of the primary tumor with curative intent within the past 7 weeks with surgical pathology demonstrating ≥ 1 of the following criteria for "intermediate" risk of recurrence:

    • Perineural invasion
    • Lymphovascular invasion
    • Single lymph node > 3 cm or ≥ 2 lymph nodes (all < 6 cm) (no extracapsular extension)
    • Close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin, and/or an initially focally positive margin that is subsequently superseded by intraoperative negative margins (similarly, patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible)
    • Pathologically confirmed T3 or T4a primary tumor
    • T2 oral cavity cancer with > 5 mm depth of invasion
  • No positive margin(s) (defined as tumor present at the cut or inked edge of the tumor), nodal extracapsular extension, and/or gross residual disease after surgery

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)
  • Total bilirubin < 2 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN
  • Serum creatinine < 2 times ULN OR creatinine clearance ≥ 50 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other invasive malignancy within the past 3 years, except for nonmelanomatous skin cancer or previously treated carcinoma in situ of the breast, oral cavity, or cervix
  • No simultaneous primary or bilateral tumors
  • No severe, active co-morbidity, including any of the following:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring IV antibiotics at the time of study registration
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
    • Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to have required oxygen therapy within the past year
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • AIDS based on current Centers for Disease Control (CDC) definition
    • Grade 3-4 electrolyte abnormalities according to CTCAE, v. 4, including any of the following:

      • Serum calcium (ionized or adjusted for albumin) < 7 mg/dL or > 12.5 mg/dL*
      • Glucose < 40 mg/dL or > 250 mg/dL
      • Magnesium < 0.9 mg/dL or > 3 mg/dL*
      • Potassium < 3.5 mmol/L or > 6 mmol/L*
      • Sodium < 130 mmol/L or > 155 mmol/L* NOTE: *Despite intervention to normalize levels.
  • No prior allergic reaction to cetuximab

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for this cancer

    • Prior chemotherapy or anti-EGF therapy for a different cancer allowed
  • No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
  • No concurrent amifostine as a radioprotector
  • No concurrent granulocyte colony-stimulating factor or erythropoietin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00956007

  Show 279 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: Mitchell Machtay, MD University Hospitals Seidman Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00956007     History of Changes
Obsolete Identifiers: NCT01311063
Other Study ID Numbers: RTOG 0920, CDR0000651536, NCI-2011-00878
Study First Received: August 8, 2009
Last Updated: May 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Radiation Therapy Oncology Group:
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage III verrucous carcinoma of the oral cavity
stage IV verrucous carcinoma of the oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
tongue cancer

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014