Clinical trial NCT00003627: Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Advanced Cancer of the Oropharynx or Hypopharynx
Official title: Phase III Randomized Study of Radiotherapy With or Without Cisplatin and Fluorouracil for Locally Advanced, Nonresectable Squamous Cell Cancer of the Oropharynx or Hypopharynx
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2003-04-30
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells and allow doctors to preserve the part of the body where the cancer started. It is not yet known whether radiation therapy with combination chemotherapy is more effective than radiation therapy alone in treating cancer of the oropharynx or hypopharynx that cannot be surgically removed.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus cisplatin and fluorouracil with radiation therapy alone in treating patients who have advanced cancer of the oropharynx or hypopharynx that cannot be surgically removed.

Detailed description: OBJECTIVES:

* Compare the overall survival and survival without relapse for 1, 3, and 5 years of patients with squamous cell cancer of the oropharynx or hypopharynx after treatment with twice a day radiotherapy with or without cisplatin and fluorouracil.
* Compare the presence of distant metastases at 1, 3, and 5 years in these patients after these treatments.
* Compare the local control and duration of control in these patients after these treatments.
* Compare the clinical changes and histological changes at 6 months in these patients after these treatments.
* Determine the rate of complete response in these patients after these treatments.
* Determine the early and late toxic effects of these regimens in these patients.
* Determine the quality of life of these patients.
* Determine the pharmacokinetics of fluorouracil and tolerability of this regimen in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and primary site of disease (oropharynx vs hypopharynx)

Patients are randomized to one of two treatment arms.

* Arm I: Patients undergo radiotherapy twice a day, 6 hours apart, 5 days a week, for 7 weeks.
* Arm II: Patients undergo radiotherapy as in arm I, plus concurrent chemotherapy consisting of cisplatin IV on day 1 and fluorouracil by continuous infusion over 24 hours on days 1-5. Courses are repeated every 3 weeks for 3 courses.

Patients are followed every month for 1 year, every 2-3 months for 2 years, then every 6 months for at least 2 years.

PROJECTED ACCRUAL: A total of 160 patients (80/arm) will be accrued for this study within 4.5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven squamous cell cancer of the oropharynx or hypopharynx

  * T4 and nonresectable OR
  * T3 extended to oropharynx or hypopharynx and nonresectable
  * N0-3 (stage III or IV)
* No distant metastases

PATIENT CHARACTERISTICS:

Age:

* 18 to 70

Performance status:

* Karnofsky 70-100%

Life expectancy:

* Greater than 3 months

Hematopoietic:

* Neutrophil count at least 2000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.25 times upper limit of normal (ULN)
* Transaminases no greater than 2.5 times ULN

Renal:

* Creatinine no greater than 1.25 times ULN

Cardiovascular:

* No severe cardiac disease

Other:

* No prior malignancy except basal cell skin cancer
* No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy
* No concurrent antineoplastic therapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy

Surgery:

* No prior surgery (except biopsy or adenectomy)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Institut J. Paoli and I. Calmettes
city: Marseille
country: France
facility: CHU de la Timone
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nantes-Saint Herblain
country: France
facility: CRLCC Nantes - Atlantique
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Reims
country: France
facility: Institut Jean Godinot
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
Study officials:
affiliation: Centre Antoine Lacassagne
name: Rene-Jean Bensadoun, MD
role: STUDY_CHAIR
References:
citation: Bensadoun RJ, Benezery K, Dassonville O, Magne N, Poissonnet G, Ramaioli A, Lemanski C, Bourdin S, Tortochaux J, Peyrade F, Marcy PY, Chamorey E, Vallicioni J, Seng H, Alzieu C, Gery B, Chauvel P, Schneider M, Santini J, Demard F, Calais G. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC). Int J Radiat Oncol Biol Phys. 2006 Mar 15;64(4):983-94. doi: 10.1016/j.ijrobp.2005.09.041. Epub 2006 Jan 10.