Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Recurrent Head and Neck Cancer That Cannot Be Removed By Surgery

Head and Neck Cancer Clinical Trial

Official title:

A Phase III Trial for Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy Versus Chemotherapy Alone

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00113399
• Other study ID #: RTOG-0421
• Secondary ID: CDR0000429480ECO
• Status: Terminated
• Phase: Phase 3
• First received: June 7, 2005
• Last updated: June 26, 2013
• Start date: April 2005

Study information

• Verified date: June 2013
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• filgrastim

Drug:
• cisplatin

• docetaxel

• fluorouracil

• paclitaxel

Radiation:
• radiation therapy

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		Date of death or last follow-up	No