Cetuximab, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Head and Neck Cancer That Cannot Be Removed By Surgery

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: NCT00646659
Recruitment Status : Terminated (Recruitment was suspended prematurely for safety concerns and closed after IDMC review)
First Posted : March 28, 2008
Last Update Posted : January 8, 2013
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

March 27, 2008
March 28, 2008
January 8, 2013
February 2008
May 2010   (Final data collection date for primary outcome measure)
Feasibility of the chemoradiotherapy part of the treatment, assessed as at least 80% dose intensity of any of the radiotherapy, the platinum, and cetuximab during the chemoradiotherapy part of the treatment
Same as current
Complete list of historical versions of study NCT00646659 on Archive Site
  • Toxicity as assessed by NCI CTCAE v3.0
  • Dose modifications
  • Response rate (complete or partial response)
  • EGFR expression and downstream signaling in primary tumor and in skin samples
Same as current
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Cetuximab, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Head and Neck Cancer That Cannot Be Removed By Surgery
Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies

RATIONALE: 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. Cetuximab may also stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high energy x- rays to kill tumor cells. Cetuximab may also make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which regimen of radiation therapy, combination chemotherapy, and cetuximab and is most effective in treating patients with head and neck cancer.

PURPOSE: This randomized phase II trial is comparing two different regimens of radiation therapy given together with combination chemotherapy and cetuximab to see how well they work in treating patients with newly diagnosed stage III or stage IV head and neck cancer that cannot be removed by surgery.


  • To determine the safety profile of chemoradiotherapy with carboplatin vs cisplatin in patients with newly diagnosed, unresectable stage III or IV squamous cell carcinoma of the head and neck.
  • To select one of these chemoradiotherapy regimens to be used as an experimental arm in a future phase III trial.
  • To look for EGFR expression and downstream signaling in reacting skin samples from patients experiencing skin toxicity and in normal skin samples from the same patients for comparison with skin samples from patients who have not shown skin toxicity.
  • To explore which factors related to EGFR predict the biological activity of cetuximab in patients treated with these regimens.

OUTLINE: This is a multicenter study.

Patients receive induction chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and fluorouracil IV continuously over 24 hours on days 1-5. Treatment repeats every 3 weeks for up to 4 courses in the absence of unacceptable toxicity.

Within 3 weeks after completion of induction chemotherapy or within 5 weeks from the start of the last chemotherapy course (day 21), patients are stratified by institution and treatment response (stable disease [SD], partial response [PR], or complete response [CR] vs non-response [progressive disease]). Patients with progressive disease are removed from study and patients with SD, PR, or CR are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo radiotherapy (RT) (3-dimensional conformal RT or intensity-modulated RT) on days 1-5 weekly for up to 7 weeks. Beginning on day 1 of RT, patients receive cisplatin IV over 1 hour once weekly for up to 7 weeks.
  • Arm II: Patients undergo RT as in arm I. Beginning on day 1 of RT, patients receive carboplatin IV over 1 hour once weekly for up to 7 weeks.

Patients in both arms receive cetuximab IV over 1-2 hours once weekly beginning on day 1 of induction chemotherapy and continuing until the end of concurrent chemoradiotherapy.

Primary tumor tissue and skin biopsies, including fixed paraffin-embedded tissue specimens or frozen tissue, are collected at baseline (prior to treatment) and after completion of study treatment for correlative laboratory studies of EGFR expression and downstream signaling. Specimens are assessed by immunohistochemistry, fluorescence in situ hybridization, and reverse transcriptase-PCR sequencing of genes and proteins for ErbB-related activation. In the event of skin toxicity during treatment, patients undergo at least two additional biopsies, one in reacting skin and one in normal skin. Samples are assessed for markers of treatment efficacy related to cetuximab.

After completion of study therapy, patients are followed at 3 months and periodically thereafter.

Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Head and Neck Cancer
  • Biological: cetuximab
  • Drug: carboplatin
  • Drug: cisplatin
  • Drug: docetaxel
  • Drug: fluorouracil
  • Genetic: fluorescence in situ hybridization
  • Genetic: molecular genetic technique
  • Genetic: reverse transcriptase-polymerase chain reaction
  • Other: immunoenzyme technique
  • Other: immunohistochemistry staining method
  • Other: laboratory biomarker analysis
  • Procedure: biopsy
  • Radiation: 3-dimensional conformal radiation therapy
  • Radiation: intensity-modulated radiation therapy
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
April 2011
May 2010   (Final data collection date for primary outcome measure)


  • Histologically confirmed newly diagnosed squamous cell carcinoma of the head and neck

    • Stage III or IV disease
    • Unresectable disease
  • Unidimensionally or bidimensionally measurable disease
  • Skin and tumor material must be available for EGFR status and downstream signaling studies
  • No nasopharyngeal, nasal, or paranasal cancer
  • No distant metastases


  • WHO performance status 0-1
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 1.5 times the upper limit of normal (ULN)
  • Alkaline phosphatase and transaminases ≤ 2.5 times ULN
  • Serum creatinine ≤ 120 μmol/L (1.36 mg/dL)
  • Creatinine clearance ≥ 60 mL/min
  • Normal cardiac function (i.e., LVEF ≥ 50%)
  • Clinically satisfactory 12-lead ECG
  • No serious cardiac illness or medical condition within the past 6 months
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No current malignancies at other sites with the exception of cone-biopsied carcinoma of the cervix and adequately treated basal or squamous cell skin carcinoma or other cancer from which the patient has been disease-free for at least the past five years
  • No unstable systemic diseases
  • No active uncontrolled infections
  • No psychological, familial, sociological, or geographical condition that would preclude compliance with the study protocol and follow-up schedule


  • See Disease Characteristics
  • No prior treatment for head and neck cancer
  • No other concurrent anticancer therapy
  • No other concurrent investigational agents
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
2006-004189-14 ( EudraCT Number )
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European Organisation for Research and Treatment of Cancer - EORTC
European Organisation for Research and Treatment of Cancer - EORTC
Not Provided
Principal Investigator: Jan B. Vermorken, MD, PhD University Hospital, Antwerp
European Organisation for Research and Treatment of Cancer - EORTC
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP