Docetaxel Based Chemotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer (DeCIDE)

Phase 3

Completed

Conditions: Cancer of the Pharynx
Cancer of the Larynx
Cancer of the Nasal Cavity
Paranasal Sinus Neoplasms
Cancer of the Oral Cavity

Interventions: Drug: docetaxel
Drug: cisplatin
Drug: hydroxyurea
Drug: fluorouracil
Procedure: chemotherapy
Procedure: radiotherapy

Registration Number: NCT00117572

Lead Sponsor: University of Chicago

Brief Summary: 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.

Detailed Description: 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 seven 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 285

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Induction plus chemoradiotherapy	chemotherapy	Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (75 mg/m2, day 1), cisplatin (75 mg/m2, day 1), and 5-fluorouracil (750 mg/m2/day, days 1-5). Total duration of 6 weeks. Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Induction plus chemoradiotherapy	radiotherapy	Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (75 mg/m2, day 1), cisplatin (75 mg/m2, day 1), and 5-fluorouracil (750 mg/m2/day, days 1-5). Total duration of 6 weeks. Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Chemoradiotherapy	docetaxel	Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Chemoradiotherapy	chemotherapy	Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Chemoradiotherapy	radiotherapy	Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Induction plus chemoradiotherapy	cisplatin	Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (75 mg/m2, day 1), cisplatin (75 mg/m2, day 1), and 5-fluorouracil (750 mg/m2/day, days 1-5). Total duration of 6 weeks. Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Induction plus chemoradiotherapy	docetaxel	Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (75 mg/m2, day 1), cisplatin (75 mg/m2, day 1), and 5-fluorouracil (750 mg/m2/day, days 1-5). Total duration of 6 weeks. Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Induction plus chemoradiotherapy	hydroxyurea	Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (75 mg/m2, day 1), cisplatin (75 mg/m2, day 1), and 5-fluorouracil (750 mg/m2/day, days 1-5). Total duration of 6 weeks. Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Induction plus chemoradiotherapy	fluorouracil	Induction therapy: Two 21-day cycles of chemotherapy consisting of docetaxel (75 mg/m2, day 1), cisplatin (75 mg/m2, day 1), and 5-fluorouracil (750 mg/m2/day, days 1-5). Total duration of 6 weeks. Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Chemoradiotherapy	hydroxyurea	Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.
Chemoradiotherapy	fluorouracil	Chemoradiotherapy: Five 14-day cycles of docetaxel (25 mg/m2, day 1), 5-fluorouracil (600 mg/m2/day, day 0-4), and hydroxyurea (500 mg PO q 12 hours x 6 days (11 doses)) with twice daily radiation (150 cGy given bid, days 1-5). Total duration of 10 weeks.

Primary Outcome Measures

Name	Time	Method
Overall Survival: Time From Randomization to Death From Any Cause	Up to 6 years	Survival rates over 6 years.

Secondary Outcome Measures

Name	Time	Method
Distant Failure-free Survival (DFFS): Time From Randomization to Distant Recurrence or Death From Any Cause	Up to 6 years	DFFS rates over 6 years. DFFS is time from randomization to distant recurrence or death from any cause
Quality of Life (McMaster)	Change from baseline to 1 year (1 year-pre)	McMaster RT Questionnaire (4-28 point scale with negative numbers indicating worsening of function)
Recurrence Free Survival: Time From Randomization to Local/Regional/Distant Recurrence or Death From Any Cause	Up to 6 years	Recurrence-free survival rates over 6 years. Recurrence-free survival is time from randomization to local, regional, or distant recurrence or death from any cause
Quality of Life (Normalcy of Diet)	Change from baseline to 1 year (1 year-pre)	Performance Status Score (0-100 point scale with negative numbers indicating worsening of function)
Quality of Life (Speech)	Change from baseline to 1 year (1 year-pre)	Performance Status Score (0-100 point scale with negative numbers indicating worsening of function)
Quality of Life (FACT H&N)	Change from baseline to 1 year (1 year-pre)	FACT Hand-and-neck subscale(b) (0-40 point scale with negative numbers indicating worsening of function)
Failure Pattern (Local/Regional Recurrence)	Up to 6 years	Percentage of patients with local/regional recurrence
Failure Pattern (Distant Recurrence)	Up to 6 years	Percentage of patients with distant recurrence

Trial Locations

Locations (26): University Hospital for Tumors Zagreb
🇭🇷
Zagreb, Croatia
Joliet Oncology Hematology Associates
🇺🇸
Joliet, Illinois, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
Roger Maris Cancer Center
🇺🇸
Fargo, North Dakota, United States
University of Tennessee Cancer Institute
🇺🇸
Memphis, Tennessee, United States
Clinique Armoricaine de Radiologie
🇫🇷
Saint Brieuc, France
Republican Oncology Dispensary
🇷🇺
UFA, Russian Federation
Hospital Clínico San Carlos
🇪🇸
Madrid, Spain
AP&S Clinic, LLC
🇺🇸
Terre Haute, Indiana, United States
Oncology Care Associates PLLC
🇺🇸
Saint Joseph, Michigan, United States
NN Blokhin Russian Cancer Research Centre RAMS
🇷🇺
Moscow, Russian Federation
Clinic of Oncology, University Hospital Center Zagreb
🇭🇷
Zagreb, Croatia
USC University of Southern California Keck School of Medicine
🇺🇸
Los Angeles, California, United States
UM Sylvester Comprehensive Cancer Center
🇺🇸
Miami, Florida, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
The University of Chicago
🇺🇸
Chicago, Illinois, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Weiss Memorial Hospital
🇺🇸
Chicago, Illinois, United States
Evanston Northwestern Healthcare
🇺🇸
Evanston, Illinois, United States
UT Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Oncology Alliance
🇺🇸
Milwaukee, Wisconsin, United States
Fort Wayne Medical Oncology/Hematology Inc.
🇺🇸
Fort Wayne, Indiana, United States
Kansas City VA Medical Center
🇺🇸
Kansas City, Missouri, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States