Know Cancer

or
forgot password

Phase III Trial of Radiotherapy Plus Cetuximab Versus Chemoradiotherapy in HPV-Associated Oropharynx Cancer


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

Thank you

Trial Information

Phase III Trial of Radiotherapy Plus Cetuximab Versus Chemoradiotherapy in HPV-Associated Oropharynx Cancer


OBJECTIVES:

Primary

- To determine whether substitution of cisplatin with cetuximab will result in comparable
5-year overall survival.

Secondary

- To monitor and compare progression-free survival for "safety".

- To compare patterns of failure (locoregional vs distant).

- To compare acute toxicity profiles (and overall toxicity burden).

- To compare overall quality of life (QOL) short-term (< 6 months) and long-term (2
years).

- To compare QOL Swallowing Domains short-term and long-term.

- To compare clinician-reported versus patient-reported CTCAE toxicity events.

- To explore differences in the cost effectiveness of cetuximab as compared to cisplatin.

- To explore differences in work status and time to return to work.

- To compare patient-reported changes in hearing.

- To compare CTCAE v. 4 late toxicity at 1, 2, and 5 years.

- To evaluate the effect of tobacco exposure (and other exposures) as measured by
standardized computer-assisted self interview (CASI) on overall survival and
progression-free survival.

- To pilot CASI collection of patient reported outcomes in a cooperative group setting.

- To determine whether specific molecular profiles are associated with overall or
progression-free survival.

- To investigate associations between changes in serum biomarkers or HPV-specific
cellular immune responses measured at baseline and three months with overall or
progression-free survival.

OUTLINE: This is a multicenter study. Patients are stratified according to T stage (T1-2 vs
T 3-4), N stage (N0-2a vs N2b-3), Zubrod performance status (0 vs 1), and smoking history (≤
10 pack-years vs > 10 pack-years). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients undergo image-guided intensity-modulated radiation therapy (IMRT) once
daily on days 1-4 and twice daily on day 5 weekly for 6 weeks. Patients also receive
high-dose cisplatin IV over 1-2 hours on days 1 and 22.

- Arm II: Beginning 1 week prior to IMRT, patients receive cetuximab IV over 2 hours.
Patients then receive cetuximab IV over 1 hour once weekly for 7 weeks. Patients
undergo IMRT as in arm I.

Tumor tissue and blood samples are collected at baseline and may also be collected at 3- and
6-month follow-up visits for correlative studies.

Patients may complete quality-of-life questionnaires and risk factors for head and neck
cancer surveys at baseline, periodically during study, and at follow-up for 1 year.

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

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Pathologically (histologically or cytologically) proven diagnosis of squamous cell
carcinoma (including the histological variants papillary squamous cell carcinoma and
basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft
palate, or oropharyngeal walls)

- No cancer from an oral cavity site (oral tongue, floor mouth, alveolar ridge,
buccal, or lip), nasopharynx, hypopharynx, or larynx, even if p16 positive

- No carcinoma of the neck of unknown primary site origin (even if p16 positive)

- Cytologic diagnosis from a cervical lymph node is sufficient in the presence of
clinical evidence of a primary tumor in the oropharynx

- Clinical evidence should be documented; may consist of palpation, imaging,
or endoscopic evaluation; and should be sufficient to estimate the size of
the primary (for T stage)

- No distant metastasis or adenopathy below the clavicles

- Patients must be positive for p16, determined by the OSU Innovation Center CLIA lab
prior to step 2 registration (randomization)

- Paraffin-embedded cytology specimens are acceptable for p16 evaluation, but
cytology smears are not

- Patients must have clinically or radiographically evident measurable disease at the
primary site or at nodal stations

- Tonsillectomy or local excision of the primary without removal of nodal disease
is permitted, as is excision removing gross nodal disease but with intact
primary site

- Limited neck dissections retrieving ≤ 4 nodes are permitted and considered as
non-therapeutic nodal excisions

- Fine-needle aspirations of the neck are insufficient due to limited tissue for
retrospective central review

- Biopsy specimens from the primary or nodes measuring at least 3-5 mm are
required

- Clinical stage T1-2 N2a-N3 or T3-4 any N, including no distant metastases

- No clinical stage T1-2 N0-1

- No simultaneous primaries or bilateral tumors

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0
g/dL is acceptable)

- Bilirubin ≤ 2 mg/dL

- AST or ALT ≤ 3 times upper limit of normal

- Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min

- Negative pregnancy test

- Women of childbearing potential and male participants must agree to use a medically
effective means of birth control throughout their participation in the treatment
phase of the study, and until at least 60 days following the last study treatment

- Patients who are HIV-positive and have no prior AIDS-defining illness and have CD4
cells of at least 340/mm³ are eligible

- HIV status must be known prior to registration

- No multidrug resistance for HIV infection

- Not seropositive for hepatitis B (hepatitis B surface antigen positive or
anti-hepatitis B core antigen positive) or hepatitis C (anti-hepatitis C antibody
positive)

- Immunity to hepatitis B (anti-hepatitis B surface antibody positive) allowed

- No prior invasive malignancy except non-melanoma skin cancer, or malignancy for which
the patient has been disease-free for at least 3 years (e.g., carcinoma in situ of
the breast, oral cavity, or cervix)

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

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

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

- Transmural myocardial infarction within the last 6 months

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days of
registration

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

- Laboratory tests for liver function and coagulation parameters are not
required for entry into this protocol

- Immunocompromised patients

- No prior allergic reaction to cisplatin or cetuximab

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior systemic chemotherapy for the study cancer

- Prior chemotherapy for a different cancer allowed

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

- No prior cetuximab or other anti-EGFR therapy

- No concurrent amifostine as a radioprotector

- No concurrent granulocyte colony-stimulating factor or erythropoietin

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

5-year overall survival

Safety Issue:

No

Principal Investigator

Andy M. Trotti, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

Unspecified

Study ID:

CDR0000695731

NCT ID:

NCT01302834

Start Date:

June 2011

Completion Date:

Related Keywords:

  • Head and Neck Cancer
  • Precancerous Condition
  • stage III squamous cell carcinoma of the oropharynx
  • stage IV squamous cell carcinoma of the oropharynx
  • human papilloma virus infection
  • Head and Neck Neoplasms
  • Precancerous Conditions
  • Oropharyngeal Neoplasms

Name

Location

Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
University of Chicago Cancer Research CenterChicago, Illinois  60637
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
Porter Adventist HospitalDenver, Colorado  80210
Swedish Medical CenterEnglewood, Colorado  80110
North Suburban Medical CenterThornton, Colorado  80229
George Bray Cancer Center at the Hospital of Central Connecticut - New Britain CampusNew Britain, Connecticut  06050
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
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
CCOP - OchsnerNew Orleans, Louisiana  70121
Rapid City Regional HospitalRapid City, South Dakota  57709
Northwest Community HospitalArlington Heights, Illinois  60005
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - GreenvilleGreenville, South Carolina  29615
University of Texas Medical BranchGalveston, Texas  77555-1329
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756-0002
Charles M. Barrett Cancer Center at University HospitalCincinnati, Ohio  45267-0526
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
CCOP - St. Louis-Cape GirardeauSaint Louis, Missouri  63141
CCOP - Virginia Mason Research CenterSeattle, Washington  98101
Utah Valley Regional Medical Center - ProvoProvo, Utah  84604
Monmouth Medical CenterLong Branch, New Jersey  07740-6395
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
City of Hope Comprehensive Cancer CenterDuarte, California  91010
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Josephine Ford Cancer Center at Henry Ford HospitalDetroit, Michigan  48202
James Graham Brown Cancer Center at University of LouisvilleLouisville, Kentucky  40202
Maine Center for Cancer Medicine and Blood Disorders - ScarboroughScarborough, Maine  04074
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Hulston Cancer Center at Cox Medical Center SouthSpringfield, Missouri  65807
Lake/University Ireland Cancer CenterMentor, Ohio  44060
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Sacred Heart Cancer Center at Sacred Heart HospitalPensacola, Florida  32504
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Mission Hospitals - Memorial CampusAsheville, North Carolina  28801
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Edwards Comprehensive Cancer Center at Cabell Huntington HospitalHuntington, West Virginia  25701
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Lahey Clinic Medical Center - BurlingtonBurlington, Massachusetts  01805
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Lourdes Regional Cancer CenterBinghamton, New York  13905
McKee Medical CenterLoveland, Colorado  80539
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Battle Creek Health System Cancer Care CenterBattle Creek, Michigan  49017
David C. Pratt Cancer Center at St. John's MercySt. Louis, Missouri  63141
Utah Cancer Specialists at UCS Cancer CenterSalt Lake City, Utah  84106
Greenebaum Cancer Center at University of Maryland Medical CenterBaltimore, Maryland  21201
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
M.D. Anderson Cancer Center at OrlandoOrlando, Florida  32806
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Butterworth Hospital at Spectrum HealthGrand Rapids, Michigan  49503-2560
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
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
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Decatur Memorial Hospital Cancer Care InstituteDecatur, Illinois  62526
Elkhart General HospitalElkhart, Indiana  46515
Cleveland Clinic Cancer Center at Fairview HospitalCleveland, Ohio  44111
Hillcrest Cancer Center at Hillcrest HospitalMayfield Heights, Ohio  44124
Rosenfeld Cancer Center at Abington Memorial HospitalAbington, Pennsylvania  19001
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
Kaiser Permanente Medical Center - South San FranciscoSouth San Francisco, California  94080
St. Francis Hospital and Health Centers - Beech Grove CampusBeech Grove, Indiana  46107
Mary Bird Perkins Cancer Center - Baton RougeBaton Rouge, Louisiana  70809
Kingsbury Center for Cancer Care at Cheshire Medical CenterKeene, New Hampshire  03431
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Highland Hospital of RochesterRochester, New York  14620
Northwest Ohio Oncology CenterMaumee, Ohio  43537
St. Charles Mercy HospitalOregon, Ohio  43616
Providence Cancer Center at Providence Portland Medical CenterPortland, Oregon  97213-2967
Providence St. Vincent Medical CenterPortland, Oregon  97225
St. Mary Regional Cancer CenterLanghorne, Pennsylvania  19047
North Star Lodge Cancer Center at Yakima Valley Memorial HospitalYakima, Washington  98902
H. Lee Moffitt Cancer Center and Research Institute at University of South FloridaTampa, Florida  33612
Northeast Georgia Medical CenterGainesville, Georgia  30501
Creticos Cancer Center at Advocate Illinois Masonic Medical CenterChicago, Illinois  60657
Cancer Center at Ball Memorial HospitalMuncie, Indiana  47303
Regional Cancer Center at Singing River HospitalPascagoula, Mississippi  39581
Moses Cone Regional Cancer Center at Wesley Long Community HospitalGreensboro, North Carolina  27401
Cancer Treatment CenterWooster, Ohio  44691
University of Miami Sylvester Comprehensive Cancer Center - MiamiMiami, Florida  33136
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/CandlerSavannah, Georgia  31405
Evanston HospitalEvanston, Illinois  60201-1781
Michiana Hematology-Oncology, PC - South BendMishawaka, Indiana  46545-1470
McFarland Clinic, PCAmes, Iowa  50010
Billings Clinic - DowntownBillings, Montana  59107-7000
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
St. Anne Mercy HospitalToledo, Ohio  43623
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
York Cancer Center at Apple Hill Medical CenterYork, Pennsylvania  17405
Jon and Karen Huntsman Cancer Center at Intermountain Medical CenterMurray, Utah  84157
Val and Ann Browning Cancer Center at McKay-Dee Hospital CenterOgden, Utah  84403
St. Joseph Cancer CenterBellingham, Washington  98225
Schiffler Cancer Center at Wheeling HospitalWheeling, West Virginia  26003
FirstHealth Moore Regional Community Hospital Comprehensive Cancer CenterPinehurst, North Carolina  28374
Regional Cancer Center at Memorial Medical CenterSpringfield, Illinois  62781-0001
John H. Stroger, Jr. Hospital of Cook CountyChicago, Illinois  60612-9985
Enloe Cancer Center at Enloe Medical CenterChico, California  95926
Radiological Associates of Sacramento Medical Group, IncorporatedSacramento, California  95815
Parkview Regional Cancer Center at Parkview HealthFort Wayne, Indiana  46805
Dubs Cancer Center at Rogue Valley Medical CenterMedford, Oregon  97504
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Theda Care Cancer InstituteAppleton, Wisconsin  54911
Kinston Medical SpecialistsKinston, North Carolina  28501
Cancer Centers of the Carolinas - Faris RoadGreenville, South Carolina  29605
Cancer Centers of the Carolinas - SpartanburgSpartanburg, South Carolina  29307
Cancer Institute at St. John's HospitalSpringfield, Illinois  62701
Sentara Cancer Institute at Sentara Norfolk General HospitalNorfolk, Virginia  23507
Providence Cancer CenterAnchorage, Alaska  99508
Lacks Cancer Center at Saint Mary's Health CareGrand Rapids, Michigan  49503
University of Wisconcin Cancer Center at Aspirus Wausau HospitalWausau, Wisconsin  54401
Solano Radiation Oncology CenterVacaville, California  95687
Integrated Community Oncology NetworkJacksonville Beach, Florida  32250
Baptist Medical Center SouthJascksonville, Florida  32258
Florida Cancer Center - PalatkaPalatka, Florida  32177
Flagler Cancer CenterSaint Augustine, Florida  32086
Mercy General HospitalSacramento, California  95819
Fountain Valley, California  92708
Dale and Frances Hughes Cancer Center at Pocono Medical CenterEast Stroudsburg, Pennsylvania  18301
Center for Cancer Care at Goshen General HospitalGoshen, Indiana  46526
Cancer Institute of Cape Girardeau, LLCCape Girardeau, Missouri  63703
Providence Cancer Center at PMCCMedford, Oregon  97504
Veterans Affairs Medical Center - MilwaukeeMilwaukee, Wisconsin  53295
Precision Radiotherapy at University PointeWest Chester, Ohio  45069
Integrated Community Oncology Network - Orange ParkOrange Park, Florida  32073
Hudner Oncology Center at Saint Anne's Hospital - Fall RiverFall River, Massachusetts  02721
NSMC Cancer Center - PeabodyPeabody, Massachusetts  01960
Georgia Cancer Center for Excellence at Grady Memorial HospitalAtlanta, Georgia  30303
Auburn Radiation OncologyAuburn, California  95603
Radiation Oncology Centers - Cameron ParkCameron Park, California  95682
Radiation Oncology Center - RosevilleRoseville, California  95661
Northwest Cancer Specialists at Vancouver Cancer CenterVancouver, Washington  98684
Mercy Cancer Center at Mercy San Juan Medical CenterCarmichael, California  95608
Kaiser Permanente - Division of Research - OaklandOakland, California  94611
Rohnert Park Cancer CenterRohnert Park, California  94928
CCOP - Kansas CityPrairie Village, Kansas  66208
St. Agnes Hospital Cancer CenterBaltimore, Maryland  21229
Barnes-Jewish West County HospitalSaint Louis, Missouri  63141
Renown Institute for Cancer at Renown Regional Medical CenterReno, Nevada  89502
Community Regional Cancer Care at Community Hospital NorthIndianapolis, Indiana  46256
Community Regional Cancer Care at Community Hospital EastIndianapolis, Indiana  46219
Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical CenterBurbank, California  91505
Integrated Community Oncology Network at Southside Cancer CenterJacksonville, Florida  32207
Southwest General Health CenterMiddleburgh Heights, Ohio  44130
UHHS Westlake Medical CenterWestlaker, Ohio  44145
Kansas City Cancer Centers - SouthwestOverland Park, Kansas  66210
Clackamas Radiation Oncology CenterClackamas, Oregon  97015
North Broward Medical CenterDearfield Beach, Florida  33064-3596
Kansas City Cancer Centers - NorthKansas City, Missouri  64154
Payson Center for Cancer Care at Concord HospitalConcord, New Hampshire  03301
Seacoast Cancer Center at Wentworth - Douglass HospitalDover, New Hampshire  03820
Nebraska Medical CenterOmaha, Nebraska  68198
Rocky Mountain Cancer Centers - AuroraAurora, Colorado  80012
Kansas City Cancer Centers - SouthKansas City, Missouri  64131
Adams Cancer CenterGettysburg, Pennsylvania  17325
Cherry Tree Cancer CenterHanover, Pennsylvania  17331
Coastal Cancer Center at Sentara Virginia Beach General HospitalVirginia Beach, Virginia  23454