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

Alternate Title

Chemotherapy and Radiation Therapy in Treating Patients With Stage III or Stage IV Larynx or Oropharynx Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	ECOG-2399 E2399, NCT00014118

Objectives

1. Determine the organ preservation rate in patients with stage III or IV squamous cell carcinoma of the larynx or oropharynx treated with paclitaxel and carboplatin followed by paclitaxel with concurrent radiotherapy.
2. Determine the feasibility and toxicity of this regimen in these patients.
3. Determine the utility of pre- and post-treatment organ function instruments on swallowing ability and voice quality in patients treated with this regimen.
4. Determine the disease-free survival and patterns of failure of patients treated with this regimen.
5. Determine the objective tumor response rate (complete and partial response) in these patients following treatment with 2 courses of induction therapy with paclitaxel and carboplatin.
6. Determine changes in quality of life of patients treated with this regimen.
7. Determine whether the presence of human papilloma virus infection and p-glycoprotein correlates with outcome in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed stage III or IV (T2-T4) squamous cell carcinoma of the larynx or oropharynx
  • No recurrent disease
  • No evidence of distant metastasis



• Resectable disease, defined as follows:
  • High probability of attaining clear surgical margins (for disease of the base of tongue, tonsil, soft palate, or pharyngeal wall)
  • No extension to root of tongue (for disease of the base of tongue)
  • No extension into pterygoid by radiograph (for disease of the tonsil, soft palate, or pharyngeal wall)
  • No primary tumor or nodal metastases fixed to the carotid artery or cervical spine (for disease of the base of tongue, tonsil, soft palate, or pharyngeal wall)
  • No trismus (for disease of the tonsil, soft palate, or pharyngeal wall)
  • No involvement of the trachea greater than 1 cm or any involvement of the esophagus (for disease of the subglottis)
  • For disease of the supraglottis, glottis, or subglottis:
    • No base of the tongue invasion greater than 2 cm
    • No tumor extension through cartilage to involve strap muscles of the neck
    • No tumor fixation to prevertebral fascia
    • No involvement of the carotid artery
    • No fixed nodal disease with involvement of the deep neck
    • Extension into pyriform sinus or lateral pharyngeal wall allowed if no extension into posterior pharynx



• Measurable disease
  • - Lesions accurately measured in at least one dimension as > 20 mm (2.0 cm) with conventional techniques or as > 10 mm (1.0 cm) with spiral CT scan
  • Cytologic or histologic evidence of neoplasm is needed for measurable disease restricted to a solitary lesion



• No other concurrent head and neck neoplasms

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy
• No concurrent amifostine

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy above the clavicles

Surgery

• No prior surgery to the primary tumor except biopsy or debulking

Other

• No concurrent experimental mucosal protectants

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Not specified

Renal

• Creatinine less than 3.0 mg/dL
• Calcium normal

Cardiovascular

• No significant cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No congestive heart failure
• No myocardial infarction within the past year
• No serious cardiac arrhythmias requiring medication

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 3 months after study completion
• No significant detectable infection
• No history of allergy to drugs containing Cremophor EL
• No history of allergy to mammalian cell-derived products (epoetin alfa) or human albumin
• No other malignancy within the past 3 years except basal or squamous cell skin cancer or carcinoma in situ of the cervix

Expected Enrollment

A total of 110 patients (55 per stratum) will be accrued for this study.

Outcomes

Organ preservation rate
Feasibility and toxicity
Utility of pre- and post-treatment organ function instruments
Disease-free survival and patterns of failure
Objective tumor response rate (complete and partial response)
Changes in quality of life
Correlation of the presence of human papilloma virus infection and p-glycoprotein with outcome

Outline

This is a multicenter study. Patients are stratified according to disease site (larynx vs oropharynx).

Patients receive induction therapy comprising paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on days 1 and 22. Within 28 days after completion of induction therapy, patients with responding or stable disease receive paclitaxel IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 and radiotherapy once daily, 5 times weekly, for 7 weeks beginning on day 1.

Within 6-8 weeks after completion of therapy, patients who initially had bulky neck disease (N3) or who have residual palpable lymphadenopathy undergo surgical neck dissection. Patients with N1-N2 disease with complete response may also undergo neck dissection. Patients with initial complete response who recur at the primary site undergo surgical salvage.

Quality of life is assessed at baseline, after induction therapy, and at 3, 12, and 24 months after completion of all therapy.

Patients are followed at 6 weeks, 3 months, every 6-8 weeks for 1 year, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 5 years thereafter.

Fakhry C, Westra WH, Li S, et al.: Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100 (4): 261-9, 2008.[PUBMED Abstract]

Cmelak AJ, Li S, Goldwasser MA, et al.: Phase II trial of chemoradiation for organ preservation in resectable stage III or IV squamous cell carcinomas of the larynx or oropharynx: results of Eastern Cooperative Oncology Group Study E2399. J Clin Oncol 25 (25): 3971-7, 2007.[PUBMED Abstract]

Fakhry C, Westra W, Li S, et al.: Prognostic significance of human papillomavirus (HPV) tumor status for patients with head and neck squamous cell carcinoma (HNSCC) in a prospective, multi-center phase II clinical trial. [Abstract] J Clin Oncol 25 (Suppl 18): A-6000, 299s, 2007.

Cmelak AJ, Li S, Murphy B, et al.: Locally advanced resectable larynx (L) or oropharynx (OP) cancer: updated results of organ preservation trial ECOG 2399. [Abstract] J Clin Oncol 24 (Suppl 18): A-5527, 286s, 2006.

Murphy BA, Smith K, Cmelak A, et al.: Swallowing function for patients treated on E2399: a phase II trial of function preservation with induction paclitaxel/carboplatin followed by radiation plus weekly paclitaxel. [Abstract] J Clin Oncol 24 (Suppl 18): A-5524, 2006.

Murphy BA, Smith K, Dowling E, et al.: Baseline swallowing function for patients treated on E2399: a phase II trial of function preservation with induction paclitaxel/carboplatin followed by radiation plus weekly paclitaxel. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2005, 2003.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Anthony Cmelak, MD, Protocol chair		Ph: 615-322-2555; 800-811-8480 Email: anthony.cmelak@vanderbilt.edu

Registry Information
Official Title		A Phase II Trial OF Chemoradiation For Organ Preservation In Resectable Stage III or IV Squamous Cell Carcinomas Of The Larynx Or Oropharynx
Trial Start Date		2001-03-16
Trial Completion Date		2009-05-11 (estimated)
Registered in ClinicalTrials.gov		NCT00014118
Date Submitted to PDQ		2001-01-03
Information Last Verified		2009-06-09
NCI Grant/Contract Number		CA21115

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