Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overNCI, OtherE3311
NCI-2013-00814, ECOG-E3311, U10CA180820, U10CA021115, NCT01898494

Trial Description

Summary

This randomized phase II trial studies how well transoral surgery followed by low-dose or standard-dose radiation therapy works in treating patients with human papilloma virus (HPV) positive stage III-IVA oropharyngeal cancer. 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. Giving radiation therapy with chemotherapy may kill any tumor cells that remain after surgery. It is not yet known how much extra treatment needs to be given after surgery.

Further Study Information

PRIMARY OBJECTIVES:

I. Accrual, risk distribution, and surgical quality will be used to determine the feasibility of a prospective multi-institutional study of transoral surgery for HPV positive (+) oropharynx cancer followed by risk-adjusted adjuvant therapy.

II. To assess the oncologic efficacy following transoral resection and adjuvant therapy in patients determined to be at "intermediate risk" after surgical excision, the 2-year progression free survival (PFS) rate will be examined.

SECONDARY OBJECTIVES:

I. To estimate the patient distribution with various histologic risk features. II. To assess and compare early and late toxicities associated with transoral surgery (TOS) and the different doses of adjuvant postoperative radiotherapy (PORT).

III. To evaluate swallowing function before and after TOS and risk-adjusted adjuvant therapy.

IV. To evaluate quality of life (QOL), swallowing perception and performance, voice outcomes, and head and neck symptoms.

TERTIARY OBJECTIVES:

I. To correlate tumor TP53 mutation and other associated mutation profile with pathologic findings, with PFS and other outcome parameters in patients with resectable HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) after the above treatments.

II. To evaluate radiation resistance markers, including excision repair cross complementing 1 (ERCC1) single nucleotide polymorphism and protein expression, and correlate them with treatment efficacy.

III. To investigate the usefulness of biomarkers in predicting progression-free survival and biomarkers, including tumor ERCC1, epidermal growth factor receptor (EGFR), plasma cytokine/chemokines, cellular immunity to HPV, and oral HPV deoxyribonucleic acid (DNA).

OUTLINE: Patients are classified by risk status (low risk, intermediate risk, or high risk) and assigned to the appropriate treatment group. Patients classified as intermediate risk are randomized to 1 or 2 treatment arms.

ARM A (low risk): Patients undergo transoral surgical resection of the oropharyngeal tumor.

ARM B (intermediate risk): Patients undergo transoral surgical resection of the oropharyngeal tumor. Patients then undergo low-dose intensity modulated radiation therapy (IMRT) once daily (QD) five days a week for 5 weeks.

ARM C (intermediate risk): Patients undergo transoral surgical resection of the oropharyngeal tumor. Patients then undergo standard-dose IMRT QD five days a week for 6 weeks.

ARM D (high risk): Patients undergo transoral surgical resection of the oropharyngeal tumor. Patients then undergo standard-dose IMRT QD five days a week for 6-7 weeks. Patients also receive cisplatin intravenously (IV) over 60 minutes or carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.

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

Eligibility Criteria

Inclusion Criteria:

  • REGISTRATION TO SURGERY (ARM S)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients must have newly diagnosed, histologically or cytologically confirmed squamous cell carcinoma or undifferentiated carcinoma of the oropharynx; patients must have been determined to have resectable oropharyngeal disease; patients with primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not eligible
  • Patients must have American Joint Committee on Cancer (AJCC) TNM tumor stage III, IV a, or IV b (with no evidence of distant metastases) as determined by imaging studies (performed < 4 weeks prior to pre-registration) and complete head and neck exam; the following imaging is required: computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI)
  • Patients must have biopsy-proven cyclin-dependent kinase inhibitor 2A (p16)+ oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may have been obtained from the primary tumor or metastatic lymph node; it is required that patients have nodal stage N1-N2b confirmed by clinical or radiographic methods (clinically N0 patients are not eligible)
  • Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory; using p16 antibody obtained from Roche mtm laboratories AG (CINtec, clone E6H4) is recommended
  • No prior radiation above the clavicles
  • Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer
  • Patients with the following within the last 6 months prior to pre-registration must be evaluated by a cardiologist and/or neurologist prior to entry into the study
  • Patients must not have evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< the upper limit of normal (ULN)
  • Calculated creatinine clearance must be > 60 ml/min using the Cockcroft-Gault formula
  • Women must not be pregnant or breast-feeding due to the teratogenicity of chemotherapy; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patient must not have an intercurrent illness likely to interfere with protocol therapy or prevent surgical resection
  • Patients must not have uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled hypertension within 30 days prior to pre-registration
  • REGISTRATION/RANDOMIZATION TO STEP 2 - ARMS A, B, C AND D AND REGISTRATION TO STEP 3
  • Histopathologic assessment of surgical pathology must include examination for perineural invasion (PNI) and lymphovascular invasion (LVI) and reported as absent or present; the absence or presence of extracapsular extension (ECE) requires gross and microscopic assessment and is defined to be:
  • Absent (negative or nodal metastasis with smooth/rounded leading edge confined to thickened capsule/pseudocapsule),
  • Present - minimal (tumor extends =< 1 mm beyond the lymph node capsule), or
  • Present - extensive (gross, tumor extends > 1 mm beyond the lymph node capsule (includes soft tissue metastasis)
  • Patients must have ECOG performance status 0 or 1
  • Patient must be registered/randomized within 5-7 weeks following surgery
  • Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

  • National Cancer Institute
Robert Ferris, Principal Investigator

Trial Sites

U.S.A.

Alabama
Birmingham

UAB Comprehensive Cancer Center

Sharon A Spencer
Ph: 205-934-0309

Arizona
Scottsdale

Mayo Clinic Scottsdale

Michael L Hinni
Ph: 507-538-7623

Arkansas
Little Rock

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Rangaswamy Govindarajan
Ph: 501-686-8274

California
Oakland

Kaiser Permanente-Oakland

Samantha A Seaward
Ph: 626-564-3455

Palo Alto

Stanford Cancer Center

Floyd C Holsinger
Ph: 650-498-7061
Email: ccto-office@stanford.edu

Colorado
Colorado Springs

Penrose Cancer Center at Penrose Hospital

Keren Sturtz
Ph: 888-785-6789

Rocky Mountain Cancer Centers at the Pavilion

Keren Sturtz
Ph: 888-785-6789

Denver

Porter Adventist Hospital

Keren Sturtz
Ph: 888-785-6789

Connecticut
New Haven

Yale Cancer Center

Benjamin L Judson
Ph: 203-785-5702

Florida
Deerfield Beach

University of Miami/Deerfield Beach

Giovana R Thomas
Ph: 866-574-5124
Email: Sylvester@emergingmed.com

Miami

University of Miami Sylvester Comprehensive Cancer Center - Miami

Giovana R Thomas
Ph: 866-574-5124
Email: Sylvester@emergingmed.com

Orlando

Florida Hospital Cancer Institute at Florida Hospital Orlando

Lee M. Zehngebot
Ph: 407-303-5623

Georgia
Atlanta

Emory University Hospital Midtown

Nabil F Saba
Ph: 404-778-1868

Winship Cancer Institute of Emory University

Nabil F Saba
Ph: 404-778-1868

Iowa
Iowa City

Holden Comprehensive Cancer Center at University of Iowa

Daniel A Vaena
Ph: 800-237-1225

Kentucky
Lexington

University of Kentucky Chandler Medical Center

Thomas J Gal
Ph: 859-257-3379

Maryland
Baltimore

Greater Baltimore Medical Center Cancer Center

Marshall A. Levine
Ph: 443-849-3706

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Jeremy D Richmon
Ph: 410-955-8804
Email: jhcccro@jhmi.edu

Massachusetts
Boston

Boston University Cancer Research Center

Scharukh Jalisi
Ph: 617-638-8265

Dana-Farber/Brigham and Women's Cancer Center

Tom Thomas
Ph: 617-724-5200

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Tom Thomas
Ph: 617-724-5200

Michigan
Detroit

Josephine Ford Cancer Center at Henry Ford Hospital

Robert Anthony Chapman
Ph: 313-916-1784

Missouri
Springfield

St. John's Regional Health Center

Jay W Carlson
Ph: 800-821-7532

Nebraska
Omaha

Fred and Pamela Buffett Cancer Center

Apar K Ganti
Ph: 402-559-6941
Email: unmcrsa@unmc.edu

Methodist Estabrook Cancer Center

Russell B. Smith
Ph: 402-354-5144

New York
Bronx

Montefiore Medical Center

Missak Haigentz
Ph: 718-904-2730
Email: aecc@aecom.yu.edu

New York

Memorial Sloan-Kettering Cancer Center

Luc G Morris
Ph: 212-639-7202

North Carolina
Durham

Duke Cancer Institute

Walter T Lee
Ph: 888-275-3853

Ohio
Cleveland

Case Comprehensive Cancer Center

David J Adelstein
Ph: 866-223-8100

Cleveland Clinic Taussig Cancer Center

David J Adelstein
Ph: 866-223-8100

Columbus

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Enver Ozer
Ph: 800-293-5066
Email: Jamesline@osumc.edu

Oregon
Portland

Knight Cancer Institute at Oregon Health and Science University

Peter E. Andersen
Ph: 503-494-1080
Email: trials@ohsu.edu

Providence Cancer Center at Providence Portland Medical Center

Alison K Conlin
Ph: 503-215-6412

Pennsylvania
Harrisburg

PinnacleHealth Regional Cancer Center at Polyclinic Hospital

Brij M Sood
Ph: 717-724-6765
Email: klitchfield@PINNACLEHEALTH.org

Philadelphia

Abramson Cancer Center of the University of Pennsylvania

Gregory S Weinstein
Ph: 800-474-9892

Fox Chase Cancer Center - Philadelphia

Miriam N Lango
Ph: 215-728-4790

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

David M Cognetti
Ph: 215-955-6084

Pittsburgh

UPMC Cancer Centers

Robert L. Ferris
Ph: 412-647-8073

South Carolina
Charleston

Hollings Cancer Center at Medical University of South Carolina

Terrence A. Day
Ph: 843-792-9321

Tennessee
Nashville

Vanderbilt-Ingram Cancer Center

James L Netterville
Ph: 800-811-8480

Texas
Dallas

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Baran D Sumer
Ph: 214-648-7097

Virginia
Hampton

Sentara Cancer Institute at Sentara CarePlex Hospital

Scott S Williams
Ph: 757-388-2406

Norfolk

Sentara Cancer Institute at Sentara Norfolk General Hospital

Scott S Williams
Ph: 757-388-2406

Virginia Beach

Coastal Cancer Center at Sentara Virginia Beach General Hospital

Scott S Williams
Ph: 757-388-2406

Washington
Seattle

University Cancer Center at University of Washington Medical Center

Eduardo Mendez
Ph: 206-616-8289

Wisconsin
Madison

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Paul M. Harari
Ph: 877-405-6866

Milwaukee

Froedtert Hospital and Medical College of Wisconsin

Stuart J. Wong
Ph: 414-805-4380

Veterans Affairs Medical Center - Milwaukee

Elizabeth M. Gore
Ph: 414-805-4380

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01898494
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.