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

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

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.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: fluorouracil; Radiation: radiation therapy; Drug: cisplatin; Drug: paclitaxel; Biological: filgrastim

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham Comprehensive Cancer Center
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • St. Joseph's Mercy Cancer Center
  • California
    • Auburn, California, United States, 95603
      • Auburn Radiation Oncology
    • Cameron Park, California, United States, 95682
      • Radiation Oncology Centers - Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy Cancer Center at Mercy San Juan Medical Center
    • Pomona, California, United States, 91767
      • Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
    • Roseville, California, United States, 95661
      • Radiation Oncology Center - Roseville
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Vacaville, California, United States, 95687
      • Solano Radiation Oncology Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Regional Cancer Center at Boca Raton Community Hospital - Main Center
    • Fort Lauderdale, Florida, United States, 33308
      • Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Jupiter, Florida, United States, 33458
      • Ella Milbank Foshay Cancer Center at Jupiter Medical Center
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • MBCCOP - Medical College of Georgia Cancer Center
    • Savannah, Georgia, United States, 31405
      • Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Aurora, Illinois, United States, 60507
      • Rush-Copley Cancer Care Center
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates, Limited - West
    • Olympia Fields, Illinois, United States, 60461
      • Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
    • Springfield, Illinois, United States, 62702
      • Cancer Institute at St. John's Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Anderson, Indiana, United States, 46016
      • St. John's Cancer Center at St. John's Medical Center
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital at Howard Regional Health System
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
    • Richmond, Indiana, United States, 47374
      • Reid Hospital & Health Care Services, Incorporated
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Louisiana
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
  • Maine
    • Waterville, Maine, United States, 04901
      • MaineGeneral Medical Center - Waterville Campus
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
    • St. Joseph, Michigan, United States, 49085
      • Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
  • Missouri
    • Cape Girardeau, Missouri, United States, 63701
      • Saint Francis Medical Center
    • Gape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
    • St Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
    • St. Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59107-7000
      • Deaconess Billings Clinic - Downtown
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center at Methodist Hospital - Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Nevada Cancer Research Foundation
  • New Hampshire
    • Keene, New Hampshire, United States, 03431
      • Kingsbury Center for Cancer Care at Cheshire Medical Center
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
    • Toms River, New Jersey, United States, 08755
      • J. Phillip Citta Regional Cancer Center at Community Medical Center
    • Vineland, New Jersey, United States, 08360
      • Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
    • Voorhees, New Jersey, United States, 08043
      • Fox Chase Virtua Health Cancer Program at Virtua West Jersey
  • New York
    • Brooklyn, New York, United States, 11201
      • Long Island College Hospital
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • Don Monti Comprehensive Cancer Center at North Shore University Hospital
    • New Hyde Park, New York, United States, 11042
      • Long Island Jewish Medical Center
  • North Carolina
    • Kinston, North Carolina, United States, 28501
      • Lenoir Memorial Cancer Center
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC
    • Bismarck, North Dakota, United States, 58501
      • Cancer Care Center at Medcenter One Hospital
    • Bismarck, North Dakota, United States, 58502
      • St. Alexius Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Akron, Ohio, United States, 44309-2090
      • Akron City Hospital
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Maumee, Ohio, United States, 43623
      • Northwest Ohio Oncology Center
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
    • Sandusky, Ohio, United States, 44870
      • Firelands Regional Medical Center
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Toledo, Ohio, United States, 43617
      • CCOP - Toledo Community Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic, Incorporated - Main Clinic
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
    • Wright-Patterson Afb, Ohio, United States, 45433-5529
      • United States Air Force Medical Center - Wright-Patterson
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Pennsylvania
    • Darby, Pennsylvania, United States, 19023
      • Mercy Fitzgerald Hospital
    • Natrona Heights, Pennsylvania, United States, 15065
      • Alle-Kiski Medical Center
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center - Philadelphia
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sioux Valley Hospital and University of South Dakota Medical Center
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
    • Salt Lake City, Utah, United States, 84143
      • Latter Day Saints Hospital
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center - North
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Comprehensive Cancer Center
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital Cancer Care Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Milwaukee, Wisconsin, United States, 53215
      • Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at Wheaton Franciscan Healthcare
    • Wausau, Wisconsin, United States, 54401
      • University of Wisconcin Cancer Center at Aspirus Wausau Hospital
    • West Milwaukee, Wisconsin, United States, 53227
      • West Allis Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Radiotherapy and chemotherapy; Radiotherapy/paclitaxel/cisplatin/filgrastim	Radiation: radiation therapy; Drug: cisplatin; Drug: paclitaxel; Biological: filgrastim
Other: Chemotherapy; Cisplatin/fluorouracil/paclitaxel/docetaxel	Drug: docetaxel; Drug: fluorouracil; Drug: cisplatin; Drug: paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	Date of death or last follow-up

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stuart J. Wong, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: June 7, 2005
• First Submitted That Met QC Criteria: June 7, 2005
• First Posted (Estimate): June 8, 2005

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: June 26, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: recurrent metastatic squamous neck cancer with occult primary; recurrent squamous cell carcinoma of the lip and oral cavity; recurrent squamous cell carcinoma of the oropharynx; recurrent lymphoepithelioma of the oropharynx; recurrent squamous cell carcinoma of the hypopharynx; recurrent squamous cell carcinoma of the larynx
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Docetaxel; Paclitaxel; Fluorouracil
• Other Study ID Numbers: RTOG-0421; CDR0000429480; ECOG-R0421