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Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Recurrent 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: NCT00113399
Recruitment Status : Terminated (Terminated early due to low accrual.)
First Posted : June 8, 2005
Results First Posted : December 31, 2012
Last Update Posted : July 2, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Radiation Therapy Oncology Group

Brief Summary:

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Cisplatin and paclitaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug (combination chemotherapy) and giving them with radiation therapy may kill more tumor cells. It is not yet known whether giving radiation therapy together with combination chemotherapy is more effective than giving combination chemotherapy alone in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy and combination chemotherapy to see how well they work compared to combination chemotherapy alone in treating patients with recurrent head and neck cancer that cannot be removed by surgery.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Biological: filgrastim Drug: cisplatin Drug: docetaxel Drug: fluorouracil Drug: paclitaxel Radiation: radiation therapy Phase 3

Detailed Description:



  • Compare overall survival of patients with previously irradiated unresectable locally recurrent squamous cell carcinoma of the head and neck treated with radiotherapy, cisplatin, and paclitaxel vs cisplatin-based chemotherapy alone.


  • Compare progression-free survival of patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Compare quality of life, functional/performance status, and quality-adjusted survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo radiotherapy twice daily and receive paclitaxel IV over 1 hour and cisplatin IV over 30 minutes once daily on days 1-5, 15-19, 29-33, and 43-47. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-13, 20-27, 34-41, and 48-55.
  • Arm II: Patients receive 1 of the following cisplatin-based* regimens at the discretion of the treating physician:

    • Regimen 1: Patients receive cisplatin* IV over 1-2 hours on day 1 and fluorouracil IV continuously over 96 hours on days 1-4.
    • Regimen 2: Patients receive cisplatin* IV over 1-2 hours and paclitaxel IV over 3 hours on day 1.
    • Regimen 3: Patients receive cisplatin* IV over 1-2 hours and docetaxel IV over 1 hour on day 1.

NOTE: *Carboplatin may be substituted for cisplatin in patients with creatinine clearance < 50 mL/min or in patients who experience grade 2 or 3 neurotoxicity.

For all regimens, treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses beyond documentation of CR.

Quality of life is assessed at baseline and then at 3, 6, 12, 24, and 36 months.

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

PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this study within 5½ years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Trial for Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy Versus Chemotherapy Alone
Study Start Date : April 2005
Actual Primary Completion Date : February 2009

Arm Intervention/treatment
Radiotherapy and chemotherapy
Biological: filgrastim
Drug: cisplatin
Drug: paclitaxel
Radiation: radiation therapy
Drug: cisplatin
Drug: docetaxel
Drug: fluorouracil
Drug: paclitaxel

Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Date of death or last follow-up ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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


  • Histologically* or cytologically* confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx, or larynx, including any of the following histologic variants:

    • Spindle cell carcinoma
    • Poorly differentiated keratin-positive carcinoma
    • Lymphoepithelioma NOTE: *Biopsy or primary tumor and/or fine needle aspiration of the metastatic lymph node required
  • Original or second primary tumor

    • Recurrent neck metastases with unknown primary allowed
  • Locally recurrent disease
  • Measurable disease
  • Unresectable disease

    • Attempted surgical resection allowed provided surgery was performed ≥ 3 months ago, wound is completely healed, and there is no sign of carotid exposure
  • Must have had prior radiotherapy for SCC of the head and neck with > 75% of the present tumor volume in areas irradiated at doses ≥ 45 Gy but ≤ 75 Gy

    • Able to successfully re-irradiate the area of the gross tumor volume without exceeding lifetime spinal cord dose of 54 Gy as determined by physical examination and CT scan and/or MRI performed within the past 8 weeks
    • First recurrence occurred > 6 months after completion of radiotherapy

      • More than 1 recurrence allowed provided the above criteria for first recurrence has been met
  • No primary tumor of the nasopharynx or salivary gland
  • No distant metastases by history or physical examination, chest CT scan, and CT scan or MRI of the tumor site

    • Patients with equivocal pulmonary nodules are eligible provided the nodules are < 1 cm, can be safely biopsied, or are negative by positron emission tomography imaging
    • No circumferential tumor involvement of the carotid sheath by imaging unless prophylactic carotid stent is placed



  • 18 and over

Performance status

  • Zubrod 0-1

Life expectancy

  • Not specified


  • Absolute neutrophil count ≥ 1,800/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)


  • AST or ALT < 2 times upper limit of normal (ULN)
  • Bilirubin < 1.5 mg/dL
  • No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects


  • Creatinine clearance > 50 mL/min
  • Calcium < 11.5 mg/dL


  • No New York Heart Association class III or IV heart disease
  • No other symptomatic or uncontrolled cardiac disease


  • No chronic obstructive pulmonary disease exacerbation
  • No other respiratory illness requiring hospitalization within the past 6 months or that would preclude study therapy


  • No AIDS
  • No prior allergic reaction to E. coli-derived products
  • No acute bacterial or fungal infection requiring IV antibiotics


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 30 days after completion of study treatment
  • No other invasive malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the breast, oral cavity, or cervix
  • No pre-existing peripheral sensory neuropathy > grade 2
  • No other severe active co-morbidity


Biologic therapy

  • Not specified


  • At least 6 months since prior chemotherapy
  • No prior systemic chemotherapy for recurrent SCC of the head and neck

    • Prior neoadjuvant, adjuvant, and/or concurrent chemotherapy and radiotherapy for initial SCC of the head and neck allowed

Endocrine therapy

  • Not specified


  • See Disease Characteristics
  • See Chemotherapy
  • At least 6 months since prior radiotherapy


  • See Disease Characteristics


  • Prior cyclooxygenase-2 inhibitor or retinoids for chemoprevention allowed
  • At least 6 months since prior epidermal growth factor receptor (EGFR) inhibitors or other targeted agents
  • No prior EGFR inhibitors or other targeted agents for recurrent SCC of the head and neck
  • No concurrent cimetidine or allopurinol (for patients on arm II, regimen 1)

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): NCT00113399

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Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
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Principal Investigator: Stuart J. Wong, MD Medical College of Wisconsin

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Responsible Party: Radiation Therapy Oncology Group Identifier: NCT00113399    
Other Study ID Numbers: RTOG-0421
First Posted: June 8, 2005    Key Record Dates
Results First Posted: December 31, 2012
Last Update Posted: July 2, 2013
Last Verified: June 2013
Keywords provided by Radiation Therapy Oncology Group:
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the oropharynx
recurrent metastatic squamous neck cancer with occult primary
recurrent lymphoepithelioma of the oropharynx
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs