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

NCT01898494 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 4 other identifiers: E3311NCI-2013-00814U10CA180820U10CA021115
• Study Type: interventional
• Target: 519
• Locations: 1 country
• Sites: 58

Brief 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.

Conditions

Human Papilloma Virus Infection; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Oropharynx

Keywords

oropharynx cancer; HPV+

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival Rate at 2 Years

  Progression-free survival is defined as the time from randomization/assignment of post-surgical treatment to the appearance of lesions, including primary, nodal or new site, or death, whichever occurs first. These patients are considered disease-free after surgery so the appearance of any lesions is counted as progression. Kaplan-Meier estimate was used to characterize progression-free survival rate at 2 years.

  Assessed every 3 months for 2 years

• Proportion of Patients With Grade III or IV Oropharyngeal Bleeding or Positive Margins

  Surgery quality was evaluated based on grade 3-4 bleeding events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 during surgery and positive margins after surgery. Per CTCAE v5.0, grade 3 = severe and grade 4 = life-threatening. Having grade 3-4 bleeding or positive margins indicates worse outcomes.

  Assessed during surgery and directly after surgery

Secondary Outcomes (4)

• Distribution of Histologic Risk Status

  Assessed after directly surgery

• Swallowing Function Before Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)

  Assessed at baseline

• Swallowing Function After Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)

  Assessed 4-6 weeks after surgery

• Quality of Life (QOL) at 6 Months After Treatment Assessed by Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-HN) Total Score

  Assessed at 6 months after treatment

Other Outcomes (3)

• Association Between TP53 Mutation and Progression-free Survival

  Assessed every 3 months for 2 years, then every 6 months, up to 5 years

• Association Between Radiation Resistance Markers and Progression-free Survival

  Assessed every 3 months for 2 year, then every 6 months, up to 5 years

• Usefulness of Biomarkers in Predicting Progression-free Survival

  Assessed every 3 months for 2 years, then every 6 months, up to 5 years

Study Arms (4)

Arm S (Surgery) then Arm A (Low risk, observation)

EXPERIMENTAL

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, low risk patients are under observation.

Procedure: Transoral surgery

Arm S (Surgery) then Arm B (Intermediate risk, low-dose IMRT)

EXPERIMENTAL

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, intermediate risk patients receive low-dose IMRT (50 Gy) QD five days a week for 5 weeks.

Procedure: Transoral surgery; Radiation: intensity-modulated radiation therapy

Arm S (Surgery) then Arm C (Intermediate risk, standard-dose IMRT)

EXPERIMENTAL

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, intermediate risk patients receive standard-dose IMRT (60 Gy) QD five days a week for 6 weeks.

Procedure: Transoral surgery; Radiation: intensity-modulated radiation therapy

Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)

EXPERIMENTAL

Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, high risk patients then receive IMRT (66Gy) QD five days a week for 6-7 weeks. Patients also receive cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.

Procedure: Transoral surgery; Radiation: intensity-modulated radiation therapy; Drug: cisplatin; Drug: carboplatin

Interventions

Transoral surgery PROCEDURE

Undergo transoral surgical resection

Also known as: TOS

Arm S (Surgery) then Arm A (Low risk, observation); Arm S (Surgery) then Arm B (Intermediate risk, low-dose IMRT); Arm S (Surgery) then Arm C (Intermediate risk, standard-dose IMRT); Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)

intensity-modulated radiation therapy RADIATION

Undergo standard-dose or low-dose IMRT

Also known as: IMRT

Arm S (Surgery) then Arm B (Intermediate risk, low-dose IMRT); Arm S (Surgery) then Arm C (Intermediate risk, standard-dose IMRT); Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)

cisplatin DRUG

Given IV

Also known as: Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II), diaminedichloroplatinum, cis-platinum, CDDP, DDP, platinum, Platinol, Platinol-AQ, DACP, NSC 119875 R R

Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)

carboplatin DRUG

Given IV

Also known as: CBDCA, JM-8, NSC-241240, Paraplatin

Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \< 30 days 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 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 a positive p16 IHC (as surrogate for HPV) status from either the primary tumor or metastatic lymph node.
• 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
• 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
• Congestive heart failure \> NYHA Class II
• Cerebrovascular accident (CVA)/transient ischaemic attack (TIA)
• Unstable angina
• Myocardial infarction
• Absolute neutrophil count \>= 1,500/mm\^3
• Platelets \>= 100,000/mm\^3
• Total bilirubin =\< the upper limit of normal (ULN)

You may not qualify if:

• Registration to Surgery (Arm S)
• Prior radiation above the clavicles
• Evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging
• 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)
• Any intercurrent illness likely to interfere with protocol therapy or prevent surgical resection
• Uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled hypertension within 30 days prior to pre-registration

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (58)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Kaiser Permanente Oakland-Broadway

Oakland, California, 94611, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, 80304, United States

Location

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, 80907, United States

Location

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, 80907, United States

Location

Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Florida Hospital Orlando

Orlando, Florida, 32803, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Mercy Hospital Springfield

Springfield, Missouri, 65804, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87102, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467-2490, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

PinnacleHealth Cancer Center-Community Campus

Harrisburg, Pennsylvania, 17109, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Sentara Cancer Institute at Sentara CarePlex Hospital

Hampton, Virginia, 23666, United States

Location

Sentara Hospitals

Norfolk, Virginia, 23507, United States

Location

Sentara Virginia Beach General Hospital

Virginia Beach, Virginia, 23454, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Zablocki Veterans Administration Medical Center

Milwaukee, Wisconsin, 53295, United States

Location

Related Publications (2)

• Ferris RL, Flamand Y, Weinstein GS, Li S, Quon H, Mehra R, Garcia JJ, Chung CH, Gillison ML, Duvvuri U, O'Malley BW Jr, Ozer E, Thomas GR, Koch WM, Gross ND, Bell RB, Saba NF, Lango M, Mendez E, Burtness B. Phase II Randomized Trial of Transoral Surgery and Low-Dose Intensity Modulated Radiation Therapy in Resectable p16+ Locally Advanced Oropharynx Cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311). J Clin Oncol. 2022 Jan 10;40(2):138-149. doi: 10.1200/JCO.21.01752. Epub 2021 Oct 26.

  PMID: 34699271 RESULT

• Burtness B, Flamand Y, Quon H, Weinstein GS, Mehra R, Garcia JJ, Kim S, O'Malley BW Jr, Ozer E, Ikpeazu C, Koch WM, Gross ND, Bell RB, Patel M, Lango MN, Morris LG, Smith R, Karakla D, Richmon JD, Holsinger FC, Ferris RL. Long-Term Follow-Up of E3311, an ECOG-ACRIN Cancer Research Group Phase II Trial of Transoral Surgery and Risk-Based Adjuvant Treatment in Human Papillomavirus-Initiated Oropharynx Cancer. J Clin Oncol. 2025 Aug 10;43(23):2559-2565. doi: 10.1200/JCO-24-02550. Epub 2025 Jun 10.

  PMID: 40493877 DERIVED

MeSH Terms

Conditions

Papillomavirus Infections; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms

Interventions

Radiotherapy, Intensity-Modulated; Cisplatin; Platinum; Carboplatin

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Robert Ferris

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2013
• First Posted: July 12, 2013
• Study Start: January 22, 2014
• Primary Completion: November 30, 2020
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 1, 2026
• Results First Posted: September 28, 2022

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (58)