Clinical trial NCT00113399: Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer That Cannot Be Removed By Surgery
Official title: A Phase III Trial for Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy Versus Chemotherapy Alone
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the oropharynx
recurrent metastatic squamous neck cancer with occult primary
recurrent lymphoepithelioma of the oropharynx
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-06-08
Enrollment: 15
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: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cisplatin and paclitaxel may make tumor cells more sensitive to radiation therapy. Giving more than one drug (combination chemotherapy) and giving them with radiation therapy may kill more tumor cells. It is not yet known whether giving radiation therapy together with combination chemotherapy is more effective than giving combination chemotherapy alone in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy and combination chemotherapy to see how well they work compared to combination chemotherapy alone in treating patients with recurrent head and neck cancer that cannot be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* Compare overall survival of patients with previously irradiated unresectable locally recurrent squamous cell carcinoma of the head and neck treated with radiotherapy, cisplatin, and paclitaxel vs cisplatin-based chemotherapy alone.

Secondary

* Compare progression-free survival of patients treated with these regimens.
* Compare the toxicity of these regimens in these patients.
* Compare quality of life, functional/performance status, and quality-adjusted survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo radiotherapy twice daily and receive paclitaxel IV over 1 hour and cisplatin IV over 30 minutes once daily on days 1-5, 15-19, 29-33, and 43-47. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-13, 20-27, 34-41, and 48-55.
* Arm II: Patients receive 1 of the following cisplatin-based\* regimens at the discretion of the treating physician:

  * Regimen 1: Patients receive cisplatin\* IV over 1-2 hours on day 1 and fluorouracil IV continuously over 96 hours on days 1-4.
  * Regimen 2: Patients receive cisplatin\* IV over 1-2 hours and paclitaxel IV over 3 hours on day 1.
  * Regimen 3: Patients receive cisplatin\* IV over 1-2 hours and docetaxel IV over 1 hour on day 1.

NOTE: \*Carboplatin may be substituted for cisplatin in patients with creatinine clearance \< 50 mL/min or in patients who experience grade 2 or 3 neurotoxicity.

For all regimens, treatment repeats every 21 days for at least 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 2 additional courses beyond documentation of CR.

Quality of life is assessed at baseline and then at 3, 6, 12, 24, and 36 months.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this study within 5½ years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically\* or cytologically\* confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx, or larynx, including any of the following histologic variants:

  * Spindle cell carcinoma
  * Poorly differentiated keratin-positive carcinoma
  * Lymphoepithelioma NOTE: \*Biopsy or primary tumor and/or fine needle aspiration of the metastatic lymph node required
* Original or second primary tumor

  * Recurrent neck metastases with unknown primary allowed
* Locally recurrent disease
* Measurable disease
* Unresectable disease

  * Attempted surgical resection allowed provided surgery was performed ≥ 3 months ago, wound is completely healed, and there is no sign of carotid exposure
* Must have had prior radiotherapy for SCC of the head and neck with \> 75% of the present tumor volume in areas irradiated at doses ≥ 45 Gy but ≤ 75 Gy

  * Able to successfully re-irradiate the area of the gross tumor volume without exceeding lifetime spinal cord dose of 54 Gy as determined by physical examination and CT scan and/or MRI performed within the past 8 weeks
  * First recurrence occurred \> 6 months after completion of radiotherapy

    * More than 1 recurrence allowed provided the above criteria for first recurrence has been met
* No primary tumor of the nasopharynx or salivary gland
* No distant metastases by history or physical examination, chest CT scan, and CT scan or MRI of the tumor site

  * Patients with equivocal pulmonary nodules are eligible provided the nodules are \< 1 cm, can be safely biopsied, or are negative by positron emission tomography imaging
  * No circumferential tumor involvement of the carotid sheath by imaging unless prophylactic carotid stent is placed

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count ≥ 1,800/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)

Hepatic

* AST or ALT \< 2 times upper limit of normal (ULN)
* Bilirubin \< 1.5 mg/dL
* No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

Renal

* Creatinine clearance \> 50 mL/min
* Calcium \< 11.5 mg/dL

Cardiovascular

* No New York Heart Association class III or IV heart disease
* No other symptomatic or uncontrolled cardiac disease

Pulmonary

* No chronic obstructive pulmonary disease exacerbation
* No other respiratory illness requiring hospitalization within the past 6 months or that would preclude study therapy

Immunologic

* No AIDS
* No prior allergic reaction to E. coli-derived products
* No acute bacterial or fungal infection requiring IV antibiotics

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 30 days after completion of study treatment
* No other invasive malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the breast, oral cavity, or cervix
* No pre-existing peripheral sensory neuropathy \> grade 2
* No other severe active co-morbidity

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* At least 6 months since prior chemotherapy
* No prior systemic chemotherapy for recurrent SCC of the head and neck

  * Prior neoadjuvant, adjuvant, and/or concurrent chemotherapy and radiotherapy for initial SCC of the head and neck allowed

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics
* See Chemotherapy
* At least 6 months since prior radiotherapy

Surgery

* See Disease Characteristics

Other

* Prior cyclooxygenase-2 inhibitor or retinoids for chemoprevention allowed
* At least 6 months since prior epidermal growth factor receptor (EGFR) inhibitors or other targeted agents
* No prior EGFR inhibitors or other targeted agents for recurrent SCC of the head and neck
* No concurrent cimetidine or allopurinol (for patients on arm II, regimen 1)

Primary outcomes:
measure: Overall Survival
timeFrame: Date of death or last follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Hot Springs
country: United States
facility: St. Joseph's Mercy Cancer Center
state: Arkansas
city: Auburn
country: United States
facility: Auburn Radiation Oncology
state: California
city: Cameron Park
country: United States
facility: Radiation Oncology Centers - Cameron Park
state: California
city: Carmichael
country: United States
facility: Mercy Cancer Center at Mercy San Juan Medical Center
state: California
city: Pomona
country: United States
facility: Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
state: California
city: Roseville
country: United States
facility: Radiation Oncology Center - Roseville
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: Vacaville
country: United States
facility: Solano Radiation Oncology Center
state: California
city: Boca Raton
country: United States
facility: Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center
state: Florida
city: Fort Lauderdale
country: United States
facility: Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
state: Florida
city: Augusta
country: United States
facility: MBCCOP - Medical College of Georgia Cancer Center
state: Georgia
city: Savannah
country: United States
facility: Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
state: Georgia
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Olympia Fields
country: United States
facility: Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
state: Illinois
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
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: Anderson
country: United States
facility: St. John's Cancer Center at St. John's Medical Center
state: Indiana
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital at Howard Regional Health System
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services, Incorporated
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Shreveport
country: United States
facility: Feist-Weiller Cancer Center at Louisiana State University Health Sciences
state: Louisiana
city: Waterville
country: United States
facility: MaineGeneral Medical Center - Waterville Campus
state: Maine
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Adrian
country: United States
facility: Hickman Cancer Center at Bixby Medical Center
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Lansing
country: United States
facility: Breslin Cancer Center at Ingham Regional Medical Center
state: Michigan
city: St. Joseph
country: United States
facility: Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
state: Michigan
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Gape Girardeau
country: United States
facility: Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: St. Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: Deaconess Billings Clinic - Downtown
state: Montana
city: Omaha
country: United States
facility: Methodist Cancer Center at Methodist Hospital - Omaha
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Keene
country: United States
facility: Kingsbury Center for Cancer Care at Cheshire Medical Center
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
state: New Jersey
city: Toms River
country: United States
facility: J. Phillip Citta Regional Cancer Center at Community Medical Center
state: New Jersey
city: Vineland
country: United States
facility: Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
state: New Jersey
city: Voorhees
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua West Jersey
state: New Jersey
city: Brooklyn
country: United States
facility: Long Island College Hospital
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: Don Monti Comprehensive Cancer Center at North Shore University Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
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: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Cancer Care Center at Medcenter One Hospital
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center
state: North Dakota
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Northwest Ohio Oncology Center
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Oregon
country: United States
facility: St. Charles Mercy Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
state: Ohio
city: Sandusky
country: United States
facility: Firelands Regional Medical Center
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic, Incorporated - Main Clinic
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Wright-Patterson Afb
country: United States
facility: United States Air Force Medical Center - Wright-Patterson
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Darby
country: United States
facility: Mercy Fitzgerald Hospital
state: Pennsylvania
city: Natrona Heights
country: United States
facility: Alle-Kiski Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health Cancer Center
state: South Carolina
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
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: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sioux Valley Hospital and University of South Dakota Medical Center
state: South Dakota
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: Utah Cancer Specialists at UCS Cancer Center
state: Utah
city: Salt Lake City
country: United States
facility: Latter Day Saints Hospital
state: Utah
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center - North
state: Vermont
city: Morgantown
country: United States
facility: Mary Babb Randolph Cancer Center at West Virginia University Hospitals
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Menomonee Falls
country: United States
facility: Community Memorial Hospital Cancer Care Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Racine
country: United States
facility: All Saints Cancer Center at Wheaton Franciscan Healthcare
state: Wisconsin
city: Wausau
country: United States
facility: University of Wisconcin Cancer Center at Aspirus Wausau Hospital
state: Wisconsin
city: West Milwaukee
country: United States
facility: West Allis Memorial Hospital
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Stuart J. Wong, MD
role: PRINCIPAL_INVESTIGATOR
References: