Clinical trial NCT00268372: S0427, Combination Chemotherapy & RT in Treating Patients With Stage III or Stage IV Cancer of the Oropharynx
Official title: A Phase III Trial of Standard Fractionation Radiation and Concurrent Single Agent Cisplatin, With and Without Docetaxel, Cisplatin, and 5-Fluorouracil Induction Chemotherapy, in Patients With Advanced Oropharyngeal Squamous Cell Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-12-22
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known whether giving combination chemotherapy together with radiation therapy is more effective than giving cisplatin together with radiation therapy in treating cancer of the oropharynx.

PURPOSE: This randomized phase III trial is studying combination chemotherapy and radiation therapy to see how well they work compared to cisplatin and radiation therapy in treating patients with stage III or stage IV cancer of the oropharynx.

Detailed description: OBJECTIVES:

Primary

* Compare the overall survival of patients with previously untreated stage III or IV squamous cell carcinoma of the oropharynx treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by radiotherapy and cisplatin versus radiotherapy and cisplatin only.
* Compare the progression-free survival in patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.
* Compare the quality of life and functional status of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to primary cancer site (base of tongue vs other), nodal extent (N0-1 vs N2-3), radiotherapy plan (conventional \[2-D or 3-D conformal radiotherapy\] vs intensity modulated radiotherapy). Patients are randomized to 1 of 2 treatment arms.

* Arm I (induction chemotherapy with or without salvage surgery followed by chemoradiotherapy)

  * Induction chemotherapy with or without early salvage surgery: Patients receive docetaxel IV over 1 hour and cisplatin over 30-60 minutes on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 21 days for 1-3 courses. Patients achieving complete or partial response at the primary site after course 1 receive 2 additional courses of therapy and then proceed to chemoradiotherapy within 3-4 weeks after completion of fluorouracil administration. Patients with stable disease or surgically resectable locoregional disease progression undergo early salvage surgery and then proceed to concurrent chemoradiotherapy within 70 days after surgery. Patients with locoregional unresectable disease progression or patients who refused early salvage surgery proceed directly to concurrent chemoradiotherapy within 3-4 weeks after completion of fluorouracil administration.
  * Chemoradiotherapy: Patients undergo 2-D or 3-D conformal radiotherapy or intensity modulated radiotherapy once daily 5 days a week for 7 weeks and receive cisplatin IV over 30-60 minutes concurrently on days 1, 22, and 43\* in the absence of disease progression or unacceptable toxicity.

NOTE: \*Patients undergoing surgery before chemoradiotherapy receive cisplatin on days 1 and 22 only of a 6-week course of radiotherapy.

* Arm II (chemoradiotherapy only): Patients undergo 2-D or 3-D conformal radiotherapy or intensity modulated radiotherapy once daily 5 days a week for 7 weeks and receive cisplatin IV over 30-60 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, after completion of chemoradiotherapy, and then at 12 months after randomization.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: Approximately 398 patients (199 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed squamous cell carcinoma of the oropharynx by biopsy or fine needle aspiration of the primary lesion or neck mass

  * Selected stage III or IV disease

    * No T1-2, N1 disease
    * No T4b disease
  * No other primary tumor sites or unknown primary tumor sites
  * Previously untreated disease
* Measurable or non-measurable disease by clinical exam, CT scan or MRI
* Disease considered to be curatively resectable

  * Patients for whom surgical excision is unlikely to result in clear margins are not eligible, including patients with any of the following:

    * Gross extension of tumor to skull base (e.g., T4b disease)
    * Severe trismus
    * Pterygoid plate erosion
    * Sphenoid bone or foramen ovale involvement
    * Direct extension to involve prevertebral-fascia
    * Extension to superior nasopharynx or eustachian tube
    * Direct extension into the neck with involvement of the deep neck musculature (neck node fixation)
    * Suspected invasion (encasement) of the common or internal carotid arteries (T4b)
    * Direct extension of neck disease to involve the external skin
    * Regional metastases to the supraclavicular neck (IVB low level VB nodes)
* Disease must be appropriate for definitive radiotherapy with curative intent
* No evidence of distant metastases (M1)

  * Must have negative chest x-ray

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-1
* No myocardial infarction within the past 3 months
* No unstable or uncontrolled angina
* No active systemic infection
* Granulocyte count \> 1,500/mm\^3
* Platelet count \> 100,000/mm\^3
* Creatinine \< 1.5 mg/dL
* Bilirubin normal
* Alkaline phosphatase ≤ 2 times upper limit of normal (ULN)
* SGOT or SGPT ≤ 1.5 times ULN
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No history of hypersensitivity reaction to products containing polysorbate 80
* No medical contraindication to surgery as defined by the treating institution
* No clinically significant motor or sensory neuropathy ≥ grade 2
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I or II cancer from which the patient is in complete remission

PRIOR CONCURRENT THERAPY:

* No prior therapeutic surgery for head and neck cancer
* No prior radiotherapy
* No prior chemotherapy

Primary outcomes:
measure: Survival at 2 years
timeFrame: 2 years
Secondary outcomes:
measure: Progression-free survival by FACT-HN CTCAE v 3.0 at 2 years
timeFrame: 2 years
measure: Toxicity by CTCAE v 3.0 after induction chemotherapy or after chemotherapy and radiotherapy
timeFrame: after chemotherapy
measure: Incidence of surgical resection
timeFrame: after treatment
measure: Site of relapse
timeFrame: at relapse
measure: Quality of life by FACT-HN week 19 after first and second registration date (arm 1)
timeFrame: after first and second registrations
Other outcomes:
Locations:
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Moline
country: United States
facility: Trinity Medical Center - East
state: Illinois
city: Moline
country: United States
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Bettendorf
country: United States
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health Center
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Boston
country: United States
facility: Cancer Research Center at Boston Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Kalamazooaa
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: St. John's Regional Health Center
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Trenton
country: United States
facility: Capital Health System Regional Cancer Center
state: New Jersey
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Cancer Center
state: North Carolina
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Wilson
country: United States
facility: Wilson Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Independence
country: United States
facility: Community Oncology Group at Cleveland Clinic Cancer Center
state: Ohio
city: Lima
country: United States
facility: St. Rita's Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cleveland Clinic - Wooster
state: Ohio
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Lackland AFB
country: United States
facility: Wilford Hall Medical Center
state: Texas
city: San Antonio
country: United States
facility: Veterans Affairs Medical Center - San Antonio (Murphy)
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center
state: Texas
city: San Antonio
country: United States
facility: University Hospital - San Antonio
state: Texas
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Logan
country: United States
facility: Logan Regional Hospital
state: Utah
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Salt Lake City
country: United States
facility: Latter Day Saints Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists at UCS Cancer Center
state: Utah
Study officials:
affiliation: The Cleveland Clinic
name: David J. Adelstein, MD
role: STUDY_CHAIR
affiliation: University of Michigan Rogel Cancer Center
name: Gregory T. Wolf, MD
role: STUDY_DIRECTOR
affiliation: Veterans Affairs Medical Center - Houston
name: P. G. Shankar Giri, MD, MB, BS
role: STUDY_CHAIR
References: