The combined use of chemotherapeutic drugs with radiation has proven to be effective in improving overall survival and local control among patients with locally advanced head and neck cancer. Induction chemotherapy given before receiving local treatment has been shown to reduce the rate of distant failure. Many drugs have been found to prevent tumor cells from growing or dividing, although it has yet to be determined which agent, or specific combination of agents, is most effective in treating head and neck cancer. Docetaxel is a drug which has been reported to show promising activity in Phase II head and neck cancer studies. Therefore, the purpose of this trial is to compare the effectiveness of induction chemotherapy followed by chemoradiotherapy versus the same chemoradiotherapy alone in patients with locally advanced head and neck cancer.

Condition	Intervention	Phase
Cancer of the Pharynx Cancer of the Larynx Cancer of the Nasal Cavity Paranasal Sinus Neoplasms Cancer of the Oral Cavity	Drug: docetaxel  Drug: cisplatin  Drug: hydroxyurea  Drug: fluorouracil  Procedure: chemotherapy  Procedure: radiotherapy	Phase III

Further Study Details: 

Primary Outcomes: Overall survival
Secondary Outcomes: Distant failure-free survival (DFFS); failure pattern; progression free survival; quality of life (QOL)
Expected Total Enrollment:  400

TRIAL DESIGN:

Phase III trial of induction therapy with docetaxel followed by chemoradiotherapy versus chemoradiotherapy alone in patients with nodal stage N2 or N3 head and neck cancer

OBJECTIVES:

Primary

• To determine the effect on overall survival when induction chemotherapy is administered prior to chemoradiotherapy in patients with N2 or N3 disease.

Secondary

• To determine the effect of induction chemotherapy when administered prior to chemoradiotherapy on distant failure-free survival, failure pattern, progression free survival and quality of life.

TREATMENT PLAN:

• After eligibility is confirmed, patients will be randomized to one of two treatment arms:

Arm A - Induction + chemoradiotherapy

Arm B - Chemoradiotherapy alone

• Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (day 1), cisplatin (day 1), and 5-fluorouracil (days 1-5). Total duration of 6 weeks.
• Chemoradiotherapy: Five 14-day cycles of docetaxel (day 1), 5-fluorouracil (day 0-4), and hydroxyurea (days 0-4) with twice daily radiation (days 1-5). Total duration of 10 weeks.
• All patients will undergo surgical evaluation after chemoradiation for possible neck dissection.
• Upon completion of treatment, patients will be monitored every three months during the first year, every six months during the second and third years, and annually thereafter, up to five years.
• Patients will be followed for Quality of Life (QOL) during the course of treatment, as well as annually thereafter, up to five years.

PROJECTED ACCRUAL:

• An expected sample size of 400 patients will be enrolled for this study (200 per treatment arm).

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Age 18 years or older
• Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas of the head and neck (excluding lip), or lymphoepithelioma
• No prior chemotherapy or radiotherapy
• Prior surgical therapy will consist only of incisional or excisional biopsy, and organ sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an existing primary tumor
• Karnofsky performance status of >= 70%
• Intact organ and bone marrow function
• Obtained informed consent

Exclusion Criteria:

• Demonstration of metastatic disease (i.e. M1 disease).
• Patients with a history of severe allergic reaction to docetaxel or other drugs formulated with polysorbate 80. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, 5-fluorouracil, or hydroxyurea
• Other coexisting malignancies or malignancies diagnosed within the previous 3 years with the exception of basal cell carcinoma, cervical cancer in situ, and other treated malignancies with no evidence of disease for at least 3 years.
• Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor. Any non-biopsy procedure must have taken place less than 3 months from initiating protocol treatment.
• Incomplete healing from previous surgery
• Pregnancy or breast feeding (men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary artery disease will be at the discretion of the attending physician.
• Uncontrolled active infection unless curable with treatment of their cancer.

Please refer to this study by ClinicalTrials.gov identifier  NCT00117572

Ezra E.W. Cohen, M.D.      773-702-4137    ecohen@medicine.bsd.uchicago.edu
Allison Dekker, R.N.      773-702-2068    adekker@medicine.bsd.uchicago.edu

California
      USC University of Southern California Keck School of Medicine, Los Angeles,  California,  90033,  United States; Not yet recruiting
Florida
      UM Sylvester Comprehensive Cancer Center, Miami,  Florida,  33136,  United States; Recruiting
Georgia
      Winship Cancer Institute, Emory University, Atlanta,  Georgia,  30322,  United States; Not yet recruiting
Illinois
      The University of Chicago, Chicago,  Illinois,  60637,  United States; Recruiting
      Oncology Hematology Associates of Central Illinois, Peoria,  Illinois,  61615,  United States; Not yet recruiting
      Joliet Oncology Hematology Associates, Joliet,  Illinois,  60435,  United States; Recruiting
      Evanston Northwestern Healthcare, Evanston,  Illinois,  60201,  United States; Recruiting
Kansas
      University of Kansas Cancer Center, Kansas City,  Kansas,  66160,  United States; Recruiting
Michigan
      Henry Ford Health System, Detroit,  Michigan,  48202,  United States; Recruiting
      Oncology Care Associates PLLC, St. Joseph,  Michigan,  49085,  United States; Recruiting
Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Missouri
      Kansas City VA Medical Center, Kansas City,  Missouri,  64128,  United States; Recruiting
Tennessee
      University of Tennessee Cancer Institute, Memphis,  Tennessee,  38104,  United States; Not yet recruiting
West Virginia
      West Virginia University/Mary Babb Randolph Cancer Center, Morgantown,  West Virginia,  26506,  United States; Not yet recruiting
Wisconsin
      Oncology Alliance, Milwaukee,  Wisconsin,  53215,  United States; Recruiting

Study chairs or principal investigators

Everett E. Vokes, M.D.,  Principal Investigator,  University of Chicago   
Ezra E.W. Cohen, M.D.,  Principal Investigator,  University of Chicago   

Study ID Numbers:  IRB 13362B
Record last reviewed:  April 2005
Last Updated:  July 25, 2005
Record first received:  July 6, 2005
ClinicalTrials.gov Identifier:  NCT00117572
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-07-26