Know Cancer

or
forgot password

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 Center New York, New York  10021
University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Mayo Clinic Cancer Center Rochester, Minnesota  55905
Cardinal Bernardin Cancer Center at Loyola University Medical Center Maywood, Illinois  60153-5500
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Carle Cancer Center Urbana, Illinois  61801
Penrose Cancer Center at Penrose Hospital Colorado Springs, Colorado  80933
Porter Adventist Hospital Denver, Colorado  80210
Siouxland Hematology-Oncology Associates, LLP Sioux City, Iowa  51101
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Mercy Cancer Center at Mercy Medical Center Canton, Ohio  44708
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical Center Cleveland, Ohio  44109
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, Wisconsin  53792-6164
Medical College of Wisconsin Cancer Center Milwaukee, Wisconsin  53226
Rapid City Regional Hospital Rapid City, South Dakota  57709
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570
Charles M. Barrett Cancer Center at University Hospital Cincinnati, Ohio  45267-0526
CCOP - Columbia River Oncology Program Portland, Oregon  97225
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia, Pennsylvania  19107
Cancer Research Center of Hawaii Honolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
Veterans Affairs Medical Center - Portland Portland, Oregon  97207
CCOP - Northwest Tacoma, Washington  98405-0986
Veterans Affairs Medical Center - Richmond Richmond, Virginia  23249
Rebecca and John Moores UCSD Cancer Center La Jolla, California  92093-0658
University of California Davis Cancer Center Sacramento, California  95817
City of Hope Comprehensive Cancer Center Duarte, California  91010
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center Kansas City, Kansas  66160-7353
James Graham Brown Cancer Center at University of Louisville Louisville, Kentucky  40202
Hulston Cancer Center at Cox Medical Center South Springfield, Missouri  65807
McDowell Cancer Center at Akron General Medical Center Akron, Ohio  44307
Lake/University Ireland Cancer Center Mentor, Ohio  44060
Yale Cancer Center New Haven, Connecticut  06520-8028
Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando, Florida  32803-1273
Winship Cancer Institute of Emory University Atlanta, Georgia  30322
Mission Hospitals - Memorial Campus Asheville, North Carolina  28801
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390
Lahey Clinic Medical Center - Burlington Burlington, Massachusetts  01805
Saint Peter's University Hospital New Brunswick, New Jersey  08901-1780
James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester, New York  14642
Utah Cancer Specialists at UCS Cancer Center Salt Lake City, Utah  84106
Cancer Care Northwest - Spokane South Spokane, Washington  99202
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
Lucille P. Markey Cancer Center at University of Kentucky Lexington, Kentucky  40536-0093
Tulane Cancer Center Office of Clinical Research Alexandria, Louisiana  71315-3198
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis St. Louis, Missouri  63110
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
Beth Israel Medical Center - Petrie Division New York, New York  10003-3803
Oklahoma University Cancer Institute Oklahoma City, Oklahoma  73104
Knight Cancer Institute at Oregon Health and Science University Portland, Oregon  97239-3098
M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009
Virginia Commonwealth University Massey Cancer Center Richmond, Virginia  23298-0037
Methodist Estabrook Cancer Center Omaha, Nebraska  68114-4199
Huntsman Cancer Institute at University of Utah Salt Lake City, Utah  84112
Cleveland Clinic Cancer Center at Fairview Hospital Cleveland, Ohio  44111
Hillcrest Cancer Center at Hillcrest Hospital Mayfield Heights, Ohio  44124
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest Allentown, Pennsylvania  18105
Fox Chase Cancer Center - Philadelphia Philadelphia, Pennsylvania  19111-2497
Fox Valley Hematology and Oncology - East Grant Street Appleton, Wisconsin  54911-3496
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center Boise, Idaho  83706
Ingalls Cancer Care Center at Ingalls Memorial Hospital Harvey, Illinois  60426
Highland Hospital of Rochester Rochester, New York  14620
St. Charles Mercy Hospital Oregon, Ohio  43616
North Coast Cancer Care, Incorporated Sandusky, Ohio  44870
Providence Cancer Center at Providence Portland Medical Center Portland, Oregon  97213-2967
Providence St. Vincent Medical Center Portland, Oregon  97225
Dixie Regional Medical Center - East Campus Saint George, Utah  84770
Southwest Washington Medical Center Cancer Center Vancouver, Washington  98668
William W. Backus Hospital Norwich, Connecticut  06360
Cancer Center at Ball Memorial Hospital Muncie, Indiana  47303
Regional Cancer Center at Singing River Hospital Pascagoula, Mississippi  39581
Missouri Baptist Cancer Center St. Louis, Missouri  63131
UAB Comprehensive Cancer Center Birmingham, Alabama  35294
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler Savannah, Georgia  31405
McFarland Clinic, PC Ames, Iowa  50010
Seton Cancer Institute at Saint Mary's - Saginaw Saginaw, Michigan  48601
Frederick R. and Betty M. Smith Cancer Treatment Center Sparta, New Jersey  07871
Summa Center for Cancer Care at Akron City Hospital Akron, Ohio  44309-2090
Barberton Citizens Hospital Barberton, Ohio  44203
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus, Ohio  43210-1240
Flower Hospital Cancer Center Sylvania, Ohio  43560
Legacy Good Samaritan Hospital & Comprehensive Cancer Center Portland, Oregon  97210
Salem Hospital Regional Cancer Care Services Salem, Oregon  97309-5014
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center Reading, Pennsylvania  19612-6052
York Cancer Center at Apple Hill Medical Center York, Pennsylvania  17405
Radiological Associates of Sacramento Medical Group, Incorporated Sacramento, California  95815
St. Vincent's Medical Center Bridgeport, Connecticut  06606
Queen's Cancer Institute at Queen's Medical Center Honolulu, Hawaii  96813
Parkview Regional Cancer Center at Parkview Health Fort Wayne, Indiana  46805
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Kinston Medical Specialists Kinston, North Carolina  28501
Regional Cancer Center - Erie Erie, Pennsylvania  16505
Cancer Institute at St. John's Hospital Springfield, Illinois  62701
Sentara Cancer Institute at Sentara Norfolk General Hospital Norfolk, Virginia  23507
Solano Radiation Oncology Center Vacaville, California  95687
Boston University Cancer Research Center Boston, Massachusetts  02118
Mercy General Hospital Sacramento, California  95819
Memorial Medical Center Modesto, California  95355
Hawaii Medical Center - East Honolulu, Hawaii  96817
Center for Cancer Care at Exeter Hospital Exeter, New Hampshire  03833
Dale and Frances Hughes Cancer Center at Pocono Medical Center East Stroudsburg, Pennsylvania  18301
University of Colorado Cancer Center at UC Health Sciences Center Aurora, Colorado  80045
Center for Cancer Care at Goshen General Hospital Goshen, Indiana  46526
Cancer Institute of Cape Girardeau, LLC Cape Girardeau, Missouri  63703
Veterans Affairs Medical Center - Milwaukee Milwaukee, Wisconsin  53295
Cancer Centers of North Carolina - Raleigh Raleigh, North Carolina  27607
Precision Radiotherapy at University Pointe West Chester, Ohio  45069
Central Maine Comprehensive Cancer Center at Central Maine Medical Center Lewiston, Maine  04240
Minnesota Oncology - Maplewood Maplewood, Minnesota  55109
Emory Crawford Long Hospital Atlanta, Georgia  30308
New York Oncology Hematology, PC at Albany Regional Cancer Care Albany, New York  12208
Auburn Radiation Oncology Auburn, California  95603
Radiation Oncology Centers - Cameron Park Cameron Park, California  95682
Radiation Oncology Center - Roseville Roseville, California  95661
Bassett Healthcare Regional Cancer Program at Mary Imogene Bassett Hospital Cooperstown, New York  13326
Northwest Cancer Specialists at Vancouver Cancer Center Vancouver, Washington  98684
Mercy Cancer Center at Mercy San Juan Medical Center Carmichael, California  95608
Barnes-Jewish West County Hospital Saint Louis, Missouri  63141
Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - St. Peters Saint Peters, Missouri  63376
Renown Institute for Cancer at Renown Regional Medical Center Reno, Nevada  89502
Sands Cancer Center Canandiaqua, New York  14424
University Radiation Oncology at Parkridge Hospital Rochester, New York  14626
Community Regional Cancer Care at Community Hospital North Indianapolis, Indiana  46256
Community Regional Cancer Care at Community Hospital East Indianapolis, Indiana  46219
Langlade Memorial Hospital Antigo, Wisconsin  54409
Southwest General Health Center Middleburgh Heights, Ohio  44130
Clackamas Radiation Oncology Center Clackamas, Oregon  97015
Saint Helena Hospital Saint Helena, California  94574
Radiation Oncology Associates Southwest Fort Wayne, Indiana  46804
Willamette Valley Cancer Center - Eugene Eugene, Oregon  97401
Texas Oncology, PA at Harris Center HEB Bedford, Texas  76022
Texas Oncology, PA at Texas Cancer Center - Denton South Denton, Texas  76210
Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital Fort Worth, Texas  76104
Cancer Care Centers of South Texas - Northeast San Antonio, Texas  78217
Texas Oncology, PA at Texas Cancer Center - Sherman Sherman, Texas  75090
Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land Sugar Land, Texas  77479
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Sleepy Hollow, New York  10591
Nebraska Medical Center Omaha, Nebraska  68198
Arizona Oncology - Tucson Tucson, Arizona  85704
Rocky Mountain Cancer Centers - Aurora Aurora, Colorado  80012
Adams Cancer Center Gettysburg, Pennsylvania  17325
Robinson Radiation Oncology Ravenna, Ohio  44266
Saint Elizabeth Cancer Institute at Saint Elizabeth Regional Medical Center Lincoln, Nebraska  68510
Coastal Cancer Center at Sentara Virginia Beach General Hospital Virginia Beach, Virginia  23454
Memorial Sloan-Kettering Cancer Center - Basking Ridge Basking Ridge, New Jersey  07920
Memorial Sloan-Kettering Cancer Center - Rockville Centre Rockville Centre, New York  11570
Memorial Hermann Hospital - Memorial City Houston, Texas  77024
Texas Oncology, PA - Wichita Falls Wichita Falls, Texas  76310