NCT01898494 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-04-01

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-free Survival Rate at 2 Years

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outcome · POSTED

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

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outcome · POSTED

Distribution of Histologic Risk Status

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · NOT POSTED

Association Between TP53 Mutation and Progression-free Survival

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outcome · NOT POSTED

Association Between Radiation Resistance Markers and Progression-free Survival

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outcome · NOT POSTED

Usefulness of Biomarkers in Predicting Progression-free Survival

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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 \< 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) * Calculated creatinine clearance must be \> 60 ml/min using the Cockcroft-Gault formula Registration/Randomization to Step2 - Arms A, B, C and D * 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) * Patient must be stratified/classified into one of the following risk categories (the highest risk feature assessed pathologically will determine the patient's category/treatment arm assignment): * Low Risk: T1-T2, N0-N1 AND clear (≥ 3mm) margins, AND no ECE or PNI/LVI * High Risk: Any of the following features: one or more positive margin(s) with any T stage, OR "Extensive" (\> 1mm) ECE, OR ≥ 5 metastatic lymph nodes (regardless of primary tumor margin status) * Intermediate Risk: Any of the following features: one or more "close" (\< 3mm) margin(s), OR "Minimal" (≤ 1mm) ECE, OR N2a (1 or more lymph node \> 3cm in diameter), OR N2b (2-4 lymph nodes positive, any diameter ≤ 6cm), OR with perineural invasion or lymphovascular invasion. * Unknown Risk: Patients found to have N2C or N3 disease on final pathologic analysis are at unknown risk for recurrence, but are not candidates for deintensified adjuvant therapy in this trial. These patients will be treated on Arm C. * Patients not categorized into the appropriate risk category will be considered ineligible for the study * Patient must be registered/randomized to Step 2 within a maximum of 7 weeks following surgery * Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception Exclusion Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients undergo transoral surgical resection of the oropharyngeal tumor. After transoral surgical resection of the oropharyngeal tumor, low risk patients are under observation.
intervention Names
Procedure: Transoral surgery
label
Arm S (Surgery) then Arm A (Low risk, observation)
type
EXPERIMENTAL
description
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.
intervention Names
Procedure: Transoral surgery
Radiation: intensity-modulated radiation therapy
label
Arm S (Surgery) then Arm B (Intermediate risk, low-dose IMRT)
type
EXPERIMENTAL
description
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.
intervention Names
Procedure: Transoral surgery
Radiation: intensity-modulated radiation therapy
label
Arm S (Surgery) then Arm C (Intermediate risk, standard-dose IMRT)
type
EXPERIMENTAL
description
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.
intervention Names
Procedure: Transoral surgery
Radiation: intensity-modulated radiation therapy
Drug: cisplatin
Drug: carboplatin
label
Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)
type
EXPERIMENTAL

interventions

arm Group Labels
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)
description
Undergo transoral surgical resection
name
Transoral surgery
other Names
TOS
type
PROCEDURE
arm Group Labels
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)
description
Undergo standard-dose or low-dose IMRT
name
intensity-modulated radiation therapy
other Names
IMRT
type
RADIATION
arm Group Labels
Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)
description
Given IV
name
cisplatin
other Names
Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II)
diaminedichloroplatinum
cis-platinum
CDDP
DDP
platinum
Platinol
Platinol-AQ
DACP
NSC 119875 R R
type
DRUG
arm Group Labels
Arm S (Surgery) then Arm D (High risk, IMRT, chemotherapy)
description
Given IV
name
carboplatin
other Names
CBDCA
JM-8
NSC-241240
Paraplatin
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 519
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Progression-free survival is defined as the time from registration to the appearance of new metastatic lesions or objective tumor progression or death, whichever occurs first. Kaplan-Meier estimate was used to characterize progression-free survival.
measure
Association Between TP53 Mutation and Progression-free Survival
time Frame
Assessed every 3 months for 2 years, then every 6 months, up to 5 years
description
Progression-free survival is defined as the time from registration to the appearance of new metastatic lesions or objective tumor progression or death, whichever occurs first. Kaplan-Meier estimate was used to characterize progression-free survival.
measure
Association Between Radiation Resistance Markers and Progression-free Survival
time Frame
Assessed every 3 months for 2 year, then every 6 months, up to 5 years
description
Progression-free survival is defined as the time from registration to the appearance of new metastatic lesions or objective tumor progression or death, whichever occurs first. Kaplan-Meier estimate was used to characterize progression-free survival.
measure
Usefulness of Biomarkers in Predicting Progression-free Survival
time Frame
Assessed every 3 months for 2 years, then every 6 months, up to 5 years

primary Outcomes

description
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.
measure
Progression-free Survival Rate at 2 Years
time Frame
Assessed every 3 months for 2 years
description
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.
measure
Proportion of Patients With Grade III or IV Oropharyngeal Bleeding or Positive Margins
time Frame
Assessed during surgery and directly after surgery

secondary Outcomes

description
Low Risk: T1-T2, N0-N1 AND clear (\> 3mm) margins, AND no extranodal extension (ENE) or PNI/LVI. Intermediate Risk: Any of the following features: one or more "close" (\< 3mm) margin(s), OR "Minimal" (\< 1mm) ENE, OR N2a (1 or more lymph node \>3cm in diameter), OR N2b (2-4 lymph nodes positive, any diameter \< 6cm), OR with perineural invastion or lymphovascular invasion. High Risk: Any of the following features: one or more positive margin(s) with any T stage, OR "Extensive" (\> 1mm) ENE, OR \> 5 metastatic lymph nodes (regardless of primary tumor margin status).
measure
Distribution of Histologic Risk Status
time Frame
Assessed after directly surgery
description
The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction in a 20-item written questionnaire. It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction. This instrument has been psychometrically validated in head and neck cancer patients. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life ("my swallowing impacts my day-to-day life"). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. This study reports the composite MDADI score. The summary MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).
measure
Swallowing Function Before Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)
time Frame
Assessed at baseline
description
The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction in a 20-item written questionnaire. It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction. This instrument has been psychometrically validated in head and neck cancer patients. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life ("my swallowing impacts my day-to-day life"). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. This study reports the composite MDADI score. The summary MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning).
measure
Swallowing Function After Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)
time Frame
Assessed 4-6 weeks after surgery
description
The FACT-H\&N (version 4) consists of a cancer-specific questionnaire, FACT-G, in addition to 12 H\&N cancer-specific items (the HN subscale). FACT-G is a 27-item measure that assesses general cancer quality of life. FACT-HN total score ranges between 0 and 148. The higher the score, the better the QOL.
measure
Quality of Life (QOL) at 6 Months After Treatment Assessed by Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-HN) Total Score
time Frame
Assessed at 6 months after treatment

Full study description

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.
detailed Description: 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: All patients undergo transoral surgery (TOS) in Step 1. ARM S: Patients undergo transoral resection of the oropharyngeal tumor. Then patients are classified by risk status (low risk, intermediate risk, or high risk) in Step 2 and assigned to the appropriate treatment group. Patients classified as intermediate risk are randomized to arms B or C. ARM A (low risk; observation): Patients receive observation. ARM B (intermediate risk): Patients undergo low-dose (50Gy) intensity modulated radiation therapy (IMRT) once daily (QD) over 25 fractions. ARM C (intermediate risk): Patients undergo standard-dose (60Gy) IMRT QD over 30 fractions. ARM D (high risk): Patients receive IMRT at 66 Gy QD for 33 fractions. Patients also receive cisplatin intravenously (IV) over 60 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 3 year.

Source references

references

citation
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
type
RESULT
citation
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
type
DERIVED

Source notices and limitations

Discovery and provenance

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niques were associated with inferior QOL and greater morbidity.</p> <p id="_336" tabindex="-1">A prospective multicenter trial (<a href="/clinicaltrials/NCT01898494">ECOG-3311</a> [NCT01898494]) evaluating transoral surgery approaches in human papillomavirus−positive oropharyngeal carcinoma with postoperative radiati
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inferior QOL and greater morbidity.</p> <p id="_336" tabindex="-1">A prospective multicenter trial (<a href="/clinicaltrials/NCT01898494">ECOG-3311</a> [NCT01898494]) evaluating transoral surgery approaches in human papillomavirus−positive oropharyngeal carcinoma with postoperative radiation dose de-escalation is cur
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luating de-intensification using reduced-dose radiation therapy (<a href="/clinicaltrials/NCT02254278">NRG-HN002</a> [NCT02254278] and <a href="/clinicaltrials/NCT01898494">ECOG-3311</a> [NCT01898494]) are ongoing in patients with low-risk HPV-positive oropharyngeal cancer. Cetuximab, an epidermal growth factor receptor inhibitor
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sing reduced-dose radiation therapy (<a href="/clinicaltrials/NCT02254278">NRG-HN002</a> [NCT02254278] and <a href="/clinicaltrials/NCT01898494">ECOG-3311</a> [NCT01898494]) are ongoing in patients with low-risk HPV-positive oropharyngeal cancer. Cetuximab, an epidermal growth factor receptor inhibitor, has been evaluated in two
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02254278). </li><li> Treatment de-intensification using transoral surgery followed by radiation dose de-escalation is being studied in <a href="/clinicaltrials/NCT01898494">ECOG-3311</a> (NCT01898494). </li></ol></div> </section><section id="_TrialSearch_66_sid_6"> <h3 id="_TrialSearch_66_sid_6_toc">Current Clinical Tri
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nt de-intensification using transoral surgery followed by radiation dose de-escalation is being studied in <a href="/clinicaltrials/NCT01898494">ECOG-3311</a> (NCT01898494). </li></ol></div> </section><section id="_TrialSearch_66_sid_6"> <h3 id="_TrialSearch_66_sid_6_toc">Current Clinical Trials</h3> <p id="_Trial
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Oropharyngeal Cancer Treatment (PDQ®)–Health Professional Version
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Updated: May 14, 2025
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May 14, 2025
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https://www.cancer.gov/types/head-and-neck/hp/adult/oropharyngeal-treatment-pdq

Preserved source evidence · Not medical advice