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A Phase II Trial of Induction Chemotherapy Followed by Cetuximab (Erbitux) With Low Dose vs. Standard Dose IMRT in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Head and Neck Cancer, Precancerous Condition

Thank you

Trial Information

A Phase II Trial of Induction Chemotherapy Followed by Cetuximab (Erbitux) With Low Dose vs. Standard Dose IMRT in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx


OBJECTIVES:

Primary

- To evaluate the efficacy of induction therapy comprising paclitaxel, cisplatin, and
cetuximab followed by cetuximab in combination with low-dose or standard-dose
intensity-modulated radiotherapy, as measured by 2-year progression-free survival
(PFS), in patients with HPV-associated resectable stage III-IVB squamous cell carcinoma
of the oropharynx.

Secondary

- To assess overall survival.

- To evaluate the objective response, local control, and metastatic rate.

- To evaluate early and late toxicities of treatment.

Tertiary

- To evaluate quality of life and speech and swallowing function as measured by FACT-G,
FACT-HN, and VHNSS.

- To assess the effect of treatment-induced fatigue on general physical functioning in
patients with head and neck cancer.

- To correlate functional decline with clinical, physical, and biologic correlatives.

- To evaluate radiation-resistance markers, including ERCC1 single nucleotide
polymorphism and protein expression, and to correlate them with treatment efficacy.

- To demonstrate the usefulness of biomarkers, including ERCC1, EGFR, cytokine and
chemokine markers, and plasma TGFA and TGFB levels, in predicting PFS and other outcome
parameters.

- To evaluate the correlation between the efficacy of cetuximab and polymorphisms in
FcγR-receptors.

- To evaluate functional outcome and biological parameters, including telomere length,
angiotensin-converting enzyme polymorphism, and C-reactive protein level.

OUTLINE: This is a multicenter study.

- Induction therapy: Patients receive cisplatin IV over 1 hour on day 1 and paclitaxel IV
over 3 hours and cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats
every 21 days for 3 courses. Patients then undergo evaluation of response to induction
therapy. Patients with a clinical complete response (CR) at the primary tumor site
proceed to group 1 of concurrent radiotherapy and cetuximab. Patients with a clinical
partial response (PR) or stable disease (SD) at the primary tumor site or those with
grossly positive disease at the primary tumor site proceed to group 2 of concurrent
radiotherapy and cetuximab.

- Concurrent radiotherapy and cetuximab: Treatment begins 14-21 days after the last day
of induction therapy.

- Group 1 (CR): Patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5
days per week for approximately 5 weeks (27 fractions). Patients also receive
cetuximab IV over 1-2 hours once weekly for 6 weeks.

- Group 2 (PR, SD, or grossly positive disease): Patients undergo standard-dose IMRT
5 days per week for approximately 6 weeks (33 fractions). Patients also receive
cetuximab IV over 1-2 hours once weekly for 7 weeks.

Patients complete questionnaires assessing fatigue, physical function, weight loss, quality
of life, head and neck symptom burden, and speech and swallowing function at baseline and at
1, 6, 12, and 24 months after completion of study treatment.

Tumor tissue and serum samples may be collected periodically for correlative laboratory
studies.

After completion of study treatment, patients are followed up periodically for 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx
as determined by H&E staining

- Newly diagnosed disease

- Resectable disease OR disease that is expected to become resectable after study
treatment

- Stage III, IVA, or IVB disease as determined by imaging studies (CT scan with IV
contrast or MRI required) and a complete head and neck exam

- Paraffin-embedded tumor specimen available for central confirmation of HPV-associated
disease as determined by H&E staining and in-situ hybridization (ISH) for HPV-16 and
IHC for p16

- HPV-associated disease is defined as p16 IHC-positive and/or HPV-16 ISH-positive

- Non-HPV-associated disease is defined as p16 IHC-negative

- NOTE: If there is limited tumor material, p16 IHC will be performed before HPV-16 ISH

- Measurable disease of the primary tumor or nodes by clinical and radiographic
methods, defined as a lesion that is ≥ 2 cm in at least one dimension by clinical
exam AND by radiographic exam with CT scan or MRI (or a lesion that is ≥ 1 cm in at
least one dimension if the radiographic exam utilizes spiral CT scan)

- No primary tumor or nodal metastasis fixed to the carotid artery, skull base, or
cervical spine

- No evidence of distant metastases

PATIENT CHARACTERISTICS:

- ECOG performance status 0-1

- Granulocytes ≥ 1,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Total serum bilirubin ≤ 1.5 mg/dL

- Creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of another malignancy (except for carcinoma in situ of the cervix and/or
nonmelanomatous skin cancer) unless it has been curatively treated and the patient
has been disease-free for ≥ 2 years

- Patients with any of the following within the past 6 months are eligible provided
they have been evaluated by a cardiologist and/or neurologist before study entry:

- NYHA class III-IV congestive heart failure

- Cerebrovascular accident or transient ischemic attack

- Unstable angina

- Myocardial infarction (with or without ST elevation)

- No uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled
hypertension within the past 30 days

- No concurrent illness likely to interfere with study therapy or to prevent surgical
resection

- No prior severe infusion reaction to a monoclonal antibody

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy

- No prior radiotherapy above the clavicles

- No prior surgery with curative intent for this disease (complete head and neck exam
with biopsy allowed)

- No prior therapy specifically and directly targeting the EGFR pathway

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

2-year progression-free survival

Safety Issue:

No

Principal Investigator

Shanthi Marur, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000665170

NCT ID:

NCT01084083

Start Date:

March 2010

Completion Date:

Related Keywords:

  • Head and Neck Cancer
  • Precancerous Condition
  • human papilloma virus infection
  • stage III squamous cell carcinoma of the oropharynx
  • stage IV squamous cell carcinoma of the oropharynx
  • tongue cancer
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms
  • Precancerous Conditions
  • Oropharyngeal Neoplasms

Name

Location

CCOP - WichitaWichita, Kansas  67214-3882
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical CenterGrand Junction, Colorado  81502
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
George Bray Cancer Center at the Hospital of Central Connecticut - New Britain CampusNew Britain, Connecticut  06050
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Fairview Ridges HospitalBurnsville, Minnesota  55337
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
Hutchinson Area Health CareHutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
CCOP - MeritCare HospitalFargo, North Dakota  58122
Natalie Warren Bryant Cancer Center at St. Francis HospitalTulsa, Oklahoma  74136
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
MBCCOP - LSU Health Sciences CenterNew Orleans, Louisiana  70112
Veterans Affairs Medical Center - Palo AltoPalo Alto, California  94304
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
St. Vincent Mercy Medical CenterToledo, Ohio  43608
CCOP - Toledo Community HospitalToledo, Ohio  43623-3456
Waukesha Memorial Hospital Regional Cancer CenterWaukesha, Wisconsin  53188
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
Stony Brook University Cancer CenterStony Brook, New York  11794-8174
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
Front Range Cancer SpecialistsFort Collins, Colorado  80528
UPMC Cancer CentersPittsburgh, Pennsylvania  15232
Poudre Valley HospitalFort Collins, Colorado  80524
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des MoinesWest Des Moines, Iowa  50266
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Mary Bird Perkins Cancer Center - Baton RougeBaton Rouge, Louisiana  70809
Medical Center of Louisiana - New OrleansNew Orleans, Louisiana  70112
Hickman Cancer Center at Bixby Medical CenterAdrian, Michigan  49221
Community Cancer Center of MonroeMonroe, Michigan  48162
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Wood County Oncology CenterBowling Green, Ohio  43402
Lima Memorial HospitalLima, Ohio  45804
Northwest Ohio Oncology CenterMaumee, Ohio  43537
Toledo Clinic - OregonOregon, Ohio  43616
St. Charles Mercy HospitalOregon, Ohio  43616
North Coast Cancer Care, IncorporatedSandusky, Ohio  44870
Mercy Hospital of TiffinTiffin, Ohio  44883
Toledo Clinic, Incorporated - Main ClinicToledo, Ohio  43623
Fulton County Health CenterWauseon, Ohio  43567
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294
Stanford Cancer CenterStanford, California  94305-5824
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Evanston HospitalEvanston, Illinois  60201-1781
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, PA - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - LiberalLiberal, Kansas  67905
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - PrattPratt, Kansas  67124
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Mercy Memorial Hospital - MonroeMonroe, Michigan  48162
Fergus Falls Medical Group, PAFergus Falls, Minnesota  56537
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
North Coast Cancer Care - ClydeClyde, Ohio  43410
Hematology Oncology CenterElyria, Ohio  44035
Community Cancer CenterElyria, Ohio  44035
Fisher-Titus Medical CenterNorwalk, Ohio  44857
Flower Hospital Cancer CenterSylvania, Ohio  43560
St. Anne Mercy HospitalToledo, Ohio  43623
Fredericksburg Oncology, IncorporatedFredericksburg, Virginia  22401
Regional Cancer Center at Oconomowoc Memorial HospitalOconomowoc, Wisconsin  53066
Union Hospital of Cecil CountyElkton MD, Maryland  21921
California Cancer Care, Incorporated - GreenbraeGreenbrae, California  94904
Butler Memorial HospitalButler, Pennsylvania  16001
St. Nicholas HospitalSheboygan, Wisconsin  53081
Vanderbilt-Ingram Cancer Center - Cool SpringsNashville, Tennessee  37064