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A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Head and Neck Cancer

Thank you

Trial Information

A Phase III Study of Postoperative Radiation Therapy (IMRT) +/- Cetuximab for Locally-Advanced Resected Head and Neck Cancer


OBJECTIVES:

Primary

- Determine whether the addition of cetuximab to postoperative intensity-modulated
radiotherapy (IMRT) will improve overall survival (OS) in patients with locally
advanced squamous cell carcinoma of the head and neck at intermediate risk following
surgery.

Secondary

- Assess the impact of the addition of cetuximab to postoperative IMRT on disease-free
survival (DFS) of these patients.

- Assess the impact of the addition of cetuximab to postoperative IMRT on acute and late
dysphagia, xerostomia, skin toxicity, and other toxicities according to common Toxicity
Criteria for Adverse Effects (CTCAE), v. 4 and their relationships with
patient-reported outcomes at 3, 12, and 24 months.

- Analyze tumor for epidermal growth factor receptor (EGFR), specifically the extent of
EGFR overexpression by immuno-histochemistry (IHC) and FISH analysis, EGFRvIII
expression, as well as the association of these assay data with OS and DFS.

- Analyze tumor for human papillomavirus (HPV) infection (as defined by in situ
hybridization), specifically, within the cohort of patients with oropharynx cancer, to
perform an exploratory analysis of the impact of HPV on DFS and OS of this patient
subset.

- Analyze tumor DNA for TP53 mutations as a predictor of response to cetuximab and
prognosis.

- Analyze germline DNA of polymorphic variants in EGFR intron repeats as a predictor of
response to cetuximab.

Tertiary

- Assess the impact of the addition of cetuximab to postoperative IMRT on loco-regional
control.

- Assess the impact of the addition of cetuximab to postoperative IMRT on
patient-reported quality of life, swallowing, xerostomia, and skin toxicity based on
head and neck specific instruments, including the Performance Status Scale for Head and
Neck Cancer (PSS-HN), the Functional Assessment of Cancer Therapy-Head & Neck
(FACT-H&N), the University of Michigan Xerostomia-Related Quality of Life Scale
(XeQOLS), and the Dermatology Life Quality Index (DLQI).

- Assess the impact of the addition of cetuximab to postoperative IMRT on cost-utility
analysis using the EuroQol (EQ-5D).

- Evaluate the utility of image-guided radiotherapy (IGRT) as a means of enhancing the
efficacy (i.e., loco-regional control) of IMRT while reducing the acute and/or late
toxicity (particularly xerostomia) and improving patient-reported outcomes
(particularly XeQOLS scores).

- Retrospectively compare the loco-regional control rate in patients treated with IMRT
alone (no IGRT or cetuximab) with similar patients treated with external beam
radiotherapy alone in the postoperative clinical trial Radiation Therapy Oncology Group
(RTOG)-95 01.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage
(T2-3 vs T4a), EGFR expression (high [≥ 80% of cells staining positive] vs low [< 80% of
cells staining positive] vs not evaluable), primary site of disease (oral cavity vs larynx
vs oropharynx p16+ vs oropharynx p16- vs oropharynx, p16 not evaluable), and use of
image-guided radiotherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients undergo intensity-modulated radiotherapy (IMRT) once daily 5 days a
week for 6 weeks in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients undergo IMRT as in arm I. Patients also receive cetuximab IV over 1-2
hours once weekly beginning at least 5 days prior to the start of IMRT and continuing
for 4 weeks after the completion of IMRT (for a total of 11 doses) in the absence of
disease progression or unacceptable toxicity.

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

Tissue samples are collected periodically for further laboratory analysis.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3
months for 2 years, every 6 months for 3 years, and then annually thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed squamous cell carcinoma (including variants, such as
verrucous carcinoma, spindle cell carcinoma, or carcinoma not otherwise specified) of
the head and neck, including the following subtypes:

- Oral cavity

- Oropharynx

- Larynx

- Clinical stage T1, N1-2, M0 OR T2-4a, N0-2, M0 disease based on the following
diagnostic workup within the past 8 weeks:

- General history and physical examination by a Radiation Oncologist and/or
Medical Oncologist

- Chest x-ray or chest CT scan (with or without contrast) or chest CT/PET scan
(with or without contrast)

- Must have undergone gross total resection of the primary tumor with curative intent
within the past 7 weeks with surgical pathology demonstrating ≥ 1 of the following
criteria for "intermediate" risk of recurrence:

- Perineural invasion

- Lymphovascular invasion

- Single lymph node > 3 cm or ≥ 2 lymph nodes (all < 6 cm) (no extracapsular
extension)

- Close margin(s) of resection, defined as cancer extending to within 5 mm of a
surgical margin, and/or an initially focally positive margin that is
subsequently superseded by intraoperative negative margins (similarly, patients
whose tumors had focally positive margins in the main specimen but negative
margins from re-excised samples in the region of the positive margin are
eligible)

- Pathologically confirmed T3 or T4a primary tumor

- T2 oral cavity cancer with > 5 mm depth of invasion

- No positive margin(s) (defined as tumor present at the cut or inked edge of the
tumor), nodal extracapsular extension, and/or gross residual disease after surgery

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-1

- Absolute granulocyte count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)

- Total bilirubin < 2 times upper limit of normal (ULN)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN

- Serum creatinine < 2 times ULN OR creatinine clearance ≥ 50 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other invasive malignancy within the past 3 years, except for nonmelanomatous skin
cancer or previously treated carcinoma in situ of the breast, oral cavity, or cervix

- No simultaneous primary or bilateral tumors

- No severe, active co-morbidity, including any of the following:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the past 6 months

- Transmural myocardial infarction within the past 6 months

- Acute bacterial or fungal infection requiring IV antibiotics at the time of
study registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy

- Idiopathic pulmonary fibrosis or other severe interstitial lung disease that
requires oxygen therapy or is thought to have required oxygen therapy within the
past year

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

- AIDS based on current Centers for Disease Control (CDC) definition

- Grade 3-4 electrolyte abnormalities according to CTCAE, v. 4, including any of
the following:

- Serum calcium (ionized or adjusted for albumin) < 7 mg/dL or > 12.5 mg/dL*

- Glucose < 40 mg/dL or > 250 mg/dL

- Magnesium < 0.9 mg/dL or > 3 mg/dL*

- Potassium < 3.5 mmol/L or > 6 mmol/L*

- Sodium < 130 mmol/L or > 155 mmol/L* NOTE: *Despite intervention to
normalize levels.

- No prior allergic reaction to cetuximab

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for this
cancer

- Prior chemotherapy or anti-EGF therapy for a different cancer allowed

- No prior radiotherapy to the region of the study cancer that would result in overlap
of radiotherapy fields

- No concurrent amifostine as a radioprotector

- No concurrent granulocyte colony-stimulating factor or erythropoietin

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Overall survival

Outcome Time Frame:

From randomization to date of death or last follow-up. Analysis occurs after 372 events have been reported.

Safety Issue:

No

Principal Investigator

Mitchell Machtay, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University Hospitals Seidman Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

RTOG 0920

NCT ID:

NCT00956007

Start Date:

November 2009

Completion Date:

Related Keywords:

  • Head and Neck Cancer
  • stage III squamous cell carcinoma of the larynx
  • stage III verrucous carcinoma of the larynx
  • stage IV squamous cell carcinoma of the larynx
  • stage IV verrucous carcinoma of the larynx
  • stage III squamous cell carcinoma of the lip and oral cavity
  • stage IV squamous cell carcinoma of the lip and oral cavity
  • stage III verrucous carcinoma of the oral cavity
  • stage IV verrucous carcinoma of the oral cavity
  • stage III squamous cell carcinoma of the oropharynx
  • stage IV squamous cell carcinoma of the oropharynx
  • tongue cancer
  • Head and Neck Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Carle Cancer CenterUrbana, Illinois  61801
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
Porter Adventist HospitalDenver, Colorado  80210
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Mercy Cancer Center at Mercy Medical CenterCanton, Ohio  44708
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical CenterCleveland, Ohio  44109
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
University of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadison, Wisconsin  53792-6164
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
Rapid City Regional HospitalRapid City, South Dakota  57709
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Charles M. Barrett Cancer Center at University HospitalCincinnati, Ohio  45267-0526
CCOP - Columbia River Oncology ProgramPortland, Oregon  97225
Kimmel Cancer Center at Thomas Jefferson University - PhiladelphiaPhiladelphia, Pennsylvania  19107
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Veterans Affairs Medical Center - PortlandPortland, Oregon  97207
CCOP - NorthwestTacoma, Washington  98405-0986
Veterans Affairs Medical Center - RichmondRichmond, Virginia  23249
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
University of California Davis Cancer CenterSacramento, California  95817
City of Hope Comprehensive Cancer CenterDuarte, California  91010
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
James Graham Brown Cancer Center at University of LouisvilleLouisville, Kentucky  40202
Hulston Cancer Center at Cox Medical Center SouthSpringfield, Missouri  65807
McDowell Cancer Center at Akron General Medical CenterAkron, Ohio  44307
Lake/University Ireland Cancer CenterMentor, Ohio  44060
Yale Cancer CenterNew Haven, Connecticut  06520-8028
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Mission Hospitals - Memorial CampusAsheville, North Carolina  28801
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Lahey Clinic Medical Center - BurlingtonBurlington, Massachusetts  01805
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Utah Cancer Specialists at UCS Cancer CenterSalt Lake City, Utah  84106
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical ResearchAlexandria, Louisiana  71315-3198
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Beth Israel Medical Center - Petrie DivisionNew York, New York  10003-3803
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Knight Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97239-3098
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Cleveland Clinic Cancer Center at Fairview HospitalCleveland, Ohio  44111
Hillcrest Cancer Center at Hillcrest HospitalMayfield Heights, Ohio  44124
Morgan Cancer Center at Lehigh Valley Hospital - Cedar CrestAllentown, Pennsylvania  18105
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
Fox Valley Hematology and Oncology - East Grant StreetAppleton, Wisconsin  54911-3496
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical CenterBoise, Idaho  83706
Ingalls Cancer Care Center at Ingalls Memorial HospitalHarvey, Illinois  60426
Highland Hospital of RochesterRochester, New York  14620
St. Charles Mercy HospitalOregon, Ohio  43616
North Coast Cancer Care, IncorporatedSandusky, Ohio  44870
Providence Cancer Center at Providence Portland Medical CenterPortland, Oregon  97213-2967
Providence St. Vincent Medical CenterPortland, Oregon  97225
Dixie Regional Medical Center - East CampusSaint George, Utah  84770
Southwest Washington Medical Center Cancer CenterVancouver, Washington  98668
William W. Backus HospitalNorwich, Connecticut  06360
Cancer Center at Ball Memorial HospitalMuncie, Indiana  47303
Regional Cancer Center at Singing River HospitalPascagoula, Mississippi  39581
Missouri Baptist Cancer CenterSt. Louis, Missouri  63131
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/CandlerSavannah, Georgia  31405
McFarland Clinic, PCAmes, Iowa  50010
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Frederick R. and Betty M. Smith Cancer Treatment CenterSparta, New Jersey  07871
Summa Center for Cancer Care at Akron City HospitalAkron, Ohio  44309-2090
Barberton Citizens HospitalBarberton, Ohio  44203
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Flower Hospital Cancer CenterSylvania, Ohio  43560
Legacy Good Samaritan Hospital & Comprehensive Cancer CenterPortland, Oregon  97210
Salem Hospital Regional Cancer Care ServicesSalem, Oregon  97309-5014
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
York Cancer Center at Apple Hill Medical CenterYork, Pennsylvania  17405
Radiological Associates of Sacramento Medical Group, IncorporatedSacramento, California  95815
St. Vincent's Medical CenterBridgeport, Connecticut  06606
Queen's Cancer Institute at Queen's Medical CenterHonolulu, Hawaii  96813
Parkview Regional Cancer Center at Parkview HealthFort Wayne, Indiana  46805
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Kinston Medical SpecialistsKinston, North Carolina  28501
Regional Cancer Center - ErieErie, Pennsylvania  16505
Cancer Institute at St. John's HospitalSpringfield, Illinois  62701
Sentara Cancer Institute at Sentara Norfolk General HospitalNorfolk, Virginia  23507
Solano Radiation Oncology CenterVacaville, California  95687
Boston University Cancer Research CenterBoston, Massachusetts  02118
Mercy General HospitalSacramento, California  95819
Memorial Medical CenterModesto, California  95355
Hawaii Medical Center - EastHonolulu, Hawaii  96817
Center for Cancer Care at Exeter HospitalExeter, New Hampshire  03833
Dale and Frances Hughes Cancer Center at Pocono Medical CenterEast Stroudsburg, Pennsylvania  18301
University of Colorado Cancer Center at UC Health Sciences CenterAurora, Colorado  80045
Center for Cancer Care at Goshen General HospitalGoshen, Indiana  46526
Cancer Institute of Cape Girardeau, LLCCape Girardeau, Missouri  63703
Veterans Affairs Medical Center - MilwaukeeMilwaukee, Wisconsin  53295
Cancer Centers of North Carolina - RaleighRaleigh, North Carolina  27607
Precision Radiotherapy at University PointeWest Chester, Ohio  45069
Central Maine Comprehensive Cancer Center at Central Maine Medical CenterLewiston, Maine  04240
Minnesota Oncology - MaplewoodMaplewood, Minnesota  55109
Emory Crawford Long HospitalAtlanta, Georgia  30308
New York Oncology Hematology, PC at Albany Regional Cancer CareAlbany, New York  12208
Auburn Radiation OncologyAuburn, California  95603
Radiation Oncology Centers - Cameron ParkCameron Park, California  95682
Radiation Oncology Center - RosevilleRoseville, California  95661
Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett HospitalCooperstown, New York  13326
Northwest Cancer Specialists at Vancouver Cancer CenterVancouver, Washington  98684
Mercy Cancer Center at Mercy San Juan Medical CenterCarmichael, California  95608
Barnes-Jewish West County HospitalSaint Louis, Missouri  63141
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. PetersSaint Peters, Missouri  63376
Renown Institute for Cancer at Renown Regional Medical CenterReno, Nevada  89502
Sands Cancer CenterCanandiaqua, New York  14424
University Radiation Oncology at Parkridge HospitalRochester, New York  14626
Community Regional Cancer Care at Community Hospital NorthIndianapolis, Indiana  46256
Community Regional Cancer Care at Community Hospital EastIndianapolis, Indiana  46219
Langlade Memorial HospitalAntigo, Wisconsin  54409
Southwest General Health CenterMiddleburgh Heights, Ohio  44130
Clackamas Radiation Oncology CenterClackamas, Oregon  97015
Saint Helena HospitalSaint Helena, California  94574
Radiation Oncology Associates SouthwestFort Wayne, Indiana  46804
Willamette Valley Cancer Center - EugeneEugene, Oregon  97401
Texas Oncology, PA at Harris Center HEBBedford, Texas  76022
Texas Oncology, PA at Texas Cancer Center - Denton SouthDenton, Texas  76210
Klabzuba Cancer Center at Harris Methodist Fort Worth HospitalFort Worth, Texas  76104
Cancer Care Centers of South Texas - NortheastSan Antonio, Texas  78217
Texas Oncology, PA at Texas Cancer Center - ShermanSherman, Texas  75090
Texas Oncology, PA at Texas Oncology Cancer Center Sugar LandSugar Land, Texas  77479
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital CenterSleepy Hollow, New York  10591
Nebraska Medical CenterOmaha, Nebraska  68198
Arizona Oncology - TucsonTucson, Arizona  85704
Rocky Mountain Cancer Centers - AuroraAurora, Colorado  80012
Adams Cancer CenterGettysburg, Pennsylvania  17325
Robinson Radiation OncologyRavenna, Ohio  44266
Saint Elizabeth Cancer Institute at Saint Elizabeth Regional Medical CenterLincoln, Nebraska  68510
Coastal Cancer Center at Sentara Virginia Beach General HospitalVirginia Beach, Virginia  23454
Memorial Sloan-Kettering Cancer Center - Basking RidgeBasking Ridge, New Jersey  07920
Memorial Sloan-Kettering Cancer Center - Rockville CentreRockville Centre, New York  11570
Memorial Hermann Hospital - Memorial CityHouston, Texas  77024
Texas Oncology, PA - Wichita FallsWichita Falls, Texas  76310