In English | En español
Questions About Cancer? 1-800-4-CANCER

Clinical Trials (PDQ®)

Page Options

  • Print This Page
  • Email This Document
Clinical Trial Questions?
Get Help:
1-800-4-CANCER
LiveHelp online chat

Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

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 FerrisPrincipal Investigator

Trial Sites

U.S.A.
Arizona
  Scottsdale
 Mayo Clinic Scottsdale
 Michael L Hinni Ph: 507-538-7623
California
  Los Angeles
 Jonsson Comprehensive Cancer Center at UCLA
 Abie H Mendelsohn Ph: 888-798-0719
  Stanford
 Stanford Cancer Center
 Floyd C Holsinger Ph: 650-498-7061
  Email: ccto-office@stanford.edu
Colorado
  Denver
 Porter Adventist Hospital
 Keren Sturtz Ph: 888-785-6789
Florida
  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
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
 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
  Email: sherrijr@iora.org
Nebraska
  Omaha
 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
Ohio
  Cleveland
 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: 866-627-7616
  Email: osu@emergingmed.com
Oregon
  Portland
 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
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
  Milwaukee
 Froedtert Hospital and Medical College of Wisconsin
 Stuart J. Wong Ph: 414-805-4380

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01898494
ClinicalTrials.gov processed this data on October 19, 2014

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.

Back to TopBack to Top