Chemotherapy and Radiation Therapy With or Without Panitumumab in Treating Patients Who Have Undergone Surgery for Advanced Hypopharyngeal Cancer, Oropharyngeal Cancer, Laryngeal Cancer, or Oral Cavity Cancer at High Risk of Recurrence

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01142414
Recruitment Status : Withdrawn
First Posted : June 11, 2010
Last Update Posted : January 16, 2012
Information provided by:
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Monoclonal antibodies, such as panitumumab, 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 chemotherapy given together with radiation therapy is more effective with or without panitumumab in treating patients with advanced cancer of the hypopharynx, oropharynx, larynx, or oral cavity.

PURPOSE: This randomized phase III trial is studying chemotherapy given together with radiation therapy to see how well it works compared with chemotherapy and radiation therapy given together with panitumumab in treating patients who have undergone surgery for advanced hypopharyngeal cancer, oropharyngeal cancer, laryngeal cancer, or oral cavity cancer at high risk of recurrence.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Biological: panitumumab Drug: cisplatin Drug: fluorouracil Other: laboratory biomarker analysis Procedure: adjuvant therapy Procedure: quality-of-life assessment Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy Phase 3

Detailed Description:



  • To determine if the addition of concurrently administered panitumumab to standard adjuvant chemoradiation, with 1 of 2 cisplatin-based regimens, significantly prolongs disease-free survival of patients with macroscopically completely resected, advanced squamous cell carcinoma of the hypopharynx, oropharynx, larynx, or oral cavity at high risk of recurrence.


  • To determine if the pre-surgery dose of panitumumab will alter the RNA expression of several genes and that these changes will provide additional prognostic information that can be used in future patient management. (Exploratory)
  • Measure the differences in RNA expression by RNA microarray and the results analyzed to create a gene expression classifier that will be checked for outcome prediction by association with disease free survival and down regulation of the glucose metabolism as measured by FDG-PET. (Exploratory)
  • To create a European biobank of biological samples which can be used for future research projects in this disease. (Exploratory)
  • To predict radiation-induced normal tissue toxicity based on in vitro lymphocyte apoptosis test and SNPs analysis. (Exploratory)
  • To assess the impact of radiation-induced side effects (swallowing dysfunction and xerostomia) on patient's quality of life.

OUTLINE: This is a multicenter study. Patients are stratified by treatment center, radiotherapy technique (3D-CRT vs IMRT), chemotherapy regimen (European Organization for Research and Treatment of Cancer [EORTC]) vs Arbeitsgemeinschaft Radiology Oncology [ARO] schedule), tumor location (larynx vs oropharynx vs hypopharynx vs oral cavity), pN-stage (pN0-2 vs pN3), pT-stage (pT1-2 vs pT3-4), margin/extracapsular extension (ECE) status (ECE+ and margin < 5 mm vs ECE- and margin < 5 mm vs ECE+ and margin > 5 mm), biological pre-study participation (yes vs no), p16 status (positive vs negative vs indeterminable). Patients are randomized to 1 of 2 treatment arms.

  • Arm I (chemoradiotherapy): Within 4-8 weeks of surgery, patients undergo 3D-conformal or intensity-modulated radiotherapy once daily 5 days a week in weeks 1-7. Patients also receive concurrent chemotherapy comprising either cisplatin IV over 1-2 hours on days 1, 22, and 43 (EORTC schedule) OR cisplatin IV over 1-2 hours and fluorouracil IV over 24 hours on days 1-5 and 29-33 (ARO schedule), in the absence of disease progression or unacceptable toxicity.
  • Arm II (chemoradiotherapy plus panitumumab): Within 4-8 weeks of surgery, patients undergo 3D-conformal or intensity-modulated radiotherapy and receive concurrent chemotherapy (EORTC schedule or ARO schedule) as in arm I. Patients also receive panitumumab IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43.

Blood samples are collected periodically for biomarker correlative studies and translational research. Patients complete quality-of-life EORTC questionnaires QLQ-C30, QLQ-HN35, and PSS-HN periodically.

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial on Postoperative Chemoradiation in Combination With Anti EGFR-Antibody Versus Postoperative Chemoradiation in Head and Neck Squamous Cell Carcinomas (HNSCC) With High Risk of Locoregional Recurrence

Primary Outcome Measures :
  1. Disease-free survival

Secondary Outcome Measures :
  1. Overall survival
  2. Loco-regional control
  3. Cumulative incidence of and time to distant metastases
  4. Cumulative incidence of and time to second cancers (all sites)
  5. Incidence of acute and late toxicity (CTCAE version 4.0)
  6. Health-related quality of life

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed primary squamous cell carcinoma of the hypopharynx, oropharynx, larynx, or oral cavity

    • Stage pT1-2 pN+ or pT3-4 any pN (stage III-IVB) disease
    • No distant metastases
    • No recurrent disease
  • Resectable disease

    • Has undergone surgical resection of carcinoma

      • p16 immunohistochemistry assay performed on tissue sections taken during the surgical procedure
      • No laser surgery
  • Potentially at high-risk of locoregional recurrence, defined as fulfilling ≥ 1 of the following criteria:

    • Close surgical margins (i.e., margins 1 mm to < 5 mm)
    • R1-resection (< 1 mm) (R2 resection is considered as not eligible)
    • Extracapsular nodal extension
  • No nasopharynx, nasal cavity, or paranasal sinuses carcinomas


  • WHO or ECOG performance status 0-1
  • Absolute neutrophils ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Hemoglobin ≥ 10.0 g/dL
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST< 3 times ULN
  • Alkaline phosphatase < 3 times ULN
  • Calculated creatinine clearance ≥ 60 mL/min
  • Calcium ≤ 11.5 mg/dL or 2.9 mmol/L
  • Magnesium ≥ 1.2 mg/dL or 0.5 mmol/L
  • Fertile patients must use effective contraception methods during the study and for 6 months after the last treatment dose
  • Not pregnant or nursing
  • No known allergic or hypersensitivity reaction to any of the components of the study treatment
  • No other concurrent serious illnesses or medical conditions, including any of the following:

    • History or evidence of interstitial pneumonitis or pulmonary fibrosis
    • Unstable cardiac disease despite treatment
    • NYHA class III-IV congestive heart failure
    • Clinically significant abnormal ECG or LVEF below the institutional lower limit of normal
    • Known HIV infection or other conditions of persistent immunodeficiency
    • Significant neurologic or psychiatric disorders
    • Active uncontrolled infection
    • Active disseminated intravascular coagulation
    • Symptomatic peripheral neuropathy (CTCAE 4.0 "peripheral sensory neuropathy and paresthesia") ≥ grade 2 or ototoxicity (CTCAE 4.0 "hearing impaired") ≥ grade 2, unless due to trauma or mechanical impairment due to tumor mass
    • Other serious underlying medical conditions that could impair the ability of the patient to participate in the study
  • No other malignancy within the past 5 years other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix

    • Patients who are disease-free for > 5 years allowed
  • No known drug abuse
  • No psychological, familial, sociological (e.g., severe alcohol addiction expected to hamper protocol compliance), or geographical condition potentially hampering compliance with the study protocol and follow-up schedule


  • No prior chemotherapy or radiotherapy for carcinoma of the head and neck
  • No prior radiotherapy to the head and neck region
  • No prior exposure to EGFR pathway-targeting therapy
  • No participation in another interventional clinical trial within the past 30 days
  • No concurrent granulocyte colony-stimulating factor (G-CSF) or erythropoietin
  • No other concurrent investigational drugs and/or anticancer treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01142414

Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Study Chair: Wilfried Budach, MD Heinrich-Heine University, Duesseldorf
Study Chair: Hans Langendijk University Medical Center Groningen
Study Chair: Carla Van Herpen Universitair Medisch Centrum St. Radboud - Nijmegen

Publications of Results:
Liberatoscioli C, Langendijk JA, Van Herpen C, et al.: EORTC 22071-24071: randomized, phase III trial of EGFR-antibody combined with adjuvant chemoradiation for patients with head and neck squamous cell carcinoma (HNSCC) at high risk of recurrence. [Abstract] J Clin Oncol 29 (Suppl 15): A-TPS197, 2011. Identifier: NCT01142414     History of Changes
Other Study ID Numbers: EORTC-22071-24071
First Posted: June 11, 2010    Key Record Dates
Last Update Posted: January 16, 2012
Last Verified: January 2012

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell 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 squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
tongue cancer

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Disease Attributes
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs