Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer That Cannot Be Removed By Surgery

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	18 and over	NCI	RTOG-0421 ECOG-R0421, NCT00113399

Special Category: CTSU trial, NCI Web site featured trial

Objectives

Primary

1. 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.

Secondary

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

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• 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

Radiotherapy

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

Surgery

• See Disease Characteristics

Other

• 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)

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• 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

Renal

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

Cardiovascular

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

Pulmonary

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

Immunologic

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

Other

• 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

Expected Enrollment

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

Outcomes

Survival

Progression-free survival
Grade 5 toxicity rate
Quality of life as assessed by the immediate (acute) side effects of treatment at 3 months
Quality of life as assessed by the late side effects of treatment at 6, 12, 24, and 36 months
Quality-adjusted survival

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.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Stuart Wong, MD, Principal investigator		Ph: 414-805-4603 Email: swong@mcw.edu

Registry Information
Official Title		A Phase III Trial for Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy Versus Chemotherapy Alone
Trial Start Date		2005-04-27
Trial Completion Date		2009-02-19
Registered in ClinicalTrials.gov		NCT00113399
Date Submitted to PDQ		2005-04-11
Information Last Verified		2009-02-20
NCI Grant/Contract Number		CA21661

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