Evaluating a Decreased Dose of Radiation Therapy to the Elective Neck for the Treatment of HPV-Related Oropharyngeal Cancer, ENLIGHT Trial

Elective Neck Dosing in Low Risk Oropharyngeal Human Papillomavirus-Related Cancer Treatment (ENLIGHT): A Single Arm Prospective Phase II Assessing 30 Gy Elective Neck Dose

This clinical trial evaluates how decreasing the dose of radiation to the elective neck (areas of lymph nodes not directly involved in the cancer) impacts treatment outcomes in patients with human papillomavirus (HPV)-related oropharyngeal cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Radiation therapy plays an important role in the treatment of HPV-related oropharyngeal cancer, but it also causes significant toxicities. Given the significant toxicities associated with treatment, and the excellent outcomes of HPV-related oropharyngeal cancer, researchers are attempting to identify methods to de-escalate treatment for HPV-related oropharyngeal cancer in an effort to maintain excellent treatment outcomes while reducing the risk of toxicities. Reducing the dose of radiation therapy to the lymph nodes in the neck that aren't directly involved in the cancer may improve patient quality of life while still maintaining excellent rates of cure of disease.

Study Overview

• Status: Recruiting
• Conditions: Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Computed Tomography; Radiation: Radiation Therapy; Procedure: Positron Emission Tomography; Procedure: Nasopharyngeal Laryngoscopy

Detailed Description

PRIMARY OBJECTIVE:

I. To determine 2-year locoregional progression free survival (LRPFS).

SECONDARY OBJECTIVES:

I. To determine 2-year progression free survival (PFS). II. To determine 2-year regional failure in the low-dose elective region. III. To determine 2-year overall survival (OS). IV. To determine physician-reported toxicities at 1, 3, 12-months as measured by Common Terminology Criteria for Adverse Events (CTCAE).

V. To assess patient-reported toxicities at 1, 3, 12-months as measured by Functional Assessment of Cancer Therapy - Head & Neck Radiotherapy Index (FACT-HN-Rad).

OUTLINE:

Patients receive standard dose radiation therapy to the tumor and reduced dose radiation therapy to the elective neck lymph nodes five days per week for a total of 35 fractions over 7 weeks. Patients also undergo computed tomography (CT), positron emission tomography (PET), and nasopharyngolaryngoscopy throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Coordinator; Phone Number: 312-695-1301; Email: cancer@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Principal Investigator: Laila A. Gharzai
      • Contact: Laila A. Gharzai; Phone Number: 312-694-6835; Email: laila.gharzai@northwestern.edu
    • Warrenville, Illinois, United States, 60555
      • Recruiting
      • Northwestern Medicine Warrenville
      • Contact: Laila Gharzai, MD; Phone Number: 312-694-6835; Email: cancer@northwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 3.1.1 Patients must have a histologically confirmed HPV-related OPSCC, confirmed by HPV insitu hybridization.
• 3.1.2 Patients must not have received prior treatment (i.e., no induction chemotherapy).
• 3.1.3 Patients must have evaluable disease (per RECIST v1.1 response criteria). See Section 6.
• 3.3 for the evaluation of measurable disease.
• 3.1.4 Patients must be age ≥ 18 years.
• 3.1.5 Patients must have AJCC 8 th edition Stage I-II disease, as defined by a T-classification of T1-3, and N-classification of N1-2, without metastases (M0), as defined by physical examination (including nasopharyngolaryngoscopy) and positron emission tomography (PET)
• 3.1.6 Patient must receive a staging PET scan prior to registration on study.
• 3.1.7 Patients must exhibit an ECOG performance status of 0-1. Please refer to Appendix A ECOG Performance Status Scale.
• 3.1.8 Patients may be planned to undergo RT alone or RT with concurrent chemotherapy, with chemotherapy managed at the discretion of the treating medical oncologist per standard of care.
• 3.1.9 RT is known to be teratogenic to a developing human fetus. For this reason, patients of child-bearing potential (POCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from time of informed consent, for the duration of study participation (while actively receiving RT. Should a patient become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. NOTE: A POCBP is any patient (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: • Has not undergone a hysterectomy or bilateral oophorectomy • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)
• 3.1.10 POCBP must have a negative pregnancy test prior to CT simulation or sign the Department of Radiation Oncology's pregnancy testing declination form. Note: the timing of the pregnancy test/declination form will follow the policy of the Department of Radiology and Oncology, which requires completion of pregnancy testing or signed pregnancy declination prior to CT simulation.
• 3.1.11 Patients must have the ability to understand and the willingness to sign a written informed consent document prior to registration.

Exclusion Criteria:

• 3.2.1 Patients with cT4, cN3, or cM1 disease by AJCC 8 th edition.
• 3.2.2 Patients who have had prior RT to the head/neck region that would result in overlap of RT fields. 3.2.3 Patients who have had prior major surgery to the head/neck region that could disrupt lymphatic flow.
• 3.2.4 Patients who have an uncontrolled intercurrent illness that would interfere with the receipt of RT including, but not limited to any of the following, are not eligible: • Uncontrolled connective tissue disorders (e.g. lupus, scleroderma) given potential for this to interfere with RT • Psychiatric illness/social situations that would limit compliance with study requirements • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (radiation therapy); Patients receive standard dose radiation therapy to the tumor and reduced dose radiation therapy to the elective neck lymph nodes five days per week for a total of 35 fractions over 7 weeks. Patients also undergo CT, PET, and nasopharyngolaryngoscopy throughout the trial.

Other: Questionnaire Administration; Ancillary studies; Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Radiation: Radiation Therapy; Undergo radiation therapy; Other Names: Cancer Radiotherapy; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; Energy Type; Procedure: Positron Emission Tomography; Undergo PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Nasopharyngeal Laryngoscopy; Undergo nasopharyngolaryngoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year locoregional progression free survival	Response Evaluation Criteria in Solid Tumors version 1.1 will be used to assess tumor response. The 2-year progression free survival (PFS) estimate will be reported along with the confidence interval. Log-rank tests will be used to compare PFS across predefined subgroups. Cox proportional hazards models will be applied to assess the impact of covariates such as age, sex, baseline disease severity on PFS, when appropriate.	From the beginning of radiation therapy to the first incidence of local recurrence, regional recurrence in the neck, or death, assessed at 2 years post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year PFS	Will be analyzed using the Kaplan-Meier method. Differences in survival distributions across patient subgroups will be evaluated using log-rank tests, and Cox models will be used to explore the effects of demographic and clinical variables on PFS.	From the beginning of radiation therapy to the first incidence of local recurrence, regional recurrence in the neck, distant metastasis, or death, assessed at 2 years post-treatment
2-year overall survival (OS)	Will be analyzed using the Kaplan-Meier method. Log-rank tests and Cox proportional hazards models may be used to explore differences in OS by covariates such as age, sex, and baseline disease severity when appropriate.	From the beginning of radiation therapy to death from any cause, assessed at 2 years post-treatment
Incidence of physician-reported adverse events (AEs)	Will be measured by Common Terminology Criteria for Adverse Events version 5.0. Will generate adverse event summaries, which will include maximum grade, attribution, and frequency, based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. AEs will be graded as mild, moderate, severe, or life-threatening. All reported toxicities will be summarized by toxicity type and maximum grade, and sorted by the number of patients experiencing each toxicity. For each patient, the maximum grade of a given toxicity will be determined across all timepoints. AE data will be presented using categorical analyses and descriptive summary statistics. No formal statistical hypothesis testing will be performed.	At 1, 3, and 12 months post-treatment
Incidence of patient-reported adverse events	Will be measured by Functional Assessment of Cancer Therapy - Head & Neck Radiotherapy Index.	At 1, 3, and 12 months post-treatment
2-year regional failure in the low-dose elective neck region	This will be assessed by comparing regional failures with the prior radiation plan, by overlaying radiation dose delivered to the area of nodal failure. Nodal failures in the 30 Gy volume will be considered elective neck failures.	At 2 years post-treatment

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Laila A Gharzai, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2025
• Primary Completion (Estimated): March 20, 2030
• Study Completion (Estimated): March 20, 2031

Study Registration Dates

• First Submitted: September 10, 2025
• First Submitted That Met QC Criteria: September 10, 2025
• First Posted (Actual): September 17, 2025

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Oropharyngeal Neoplasms; Investigative Techniques; Therapeutics; Physical Phenomena; Chemistry Techniques, Analytical; Spectrum Analysis; Radiotherapy; Radiation; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: NU 25N01 (Other Identifier: Northwestern University); P30CA060553 (U.S. NIH Grant/Contract); NCI-2025-06273 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); STU00224657

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No