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

NCT07178301 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 25N01NCI-2025-06273STU00224657P30CA060553
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 2-year 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 regional failure in the low-dose elective neck region

  At 2 years post-treatment

• 2-year overall survival (OS)

  From the beginning of radiation therapy to death from any cause, assessed at 2 years post-treatment

• Incidence of physician-reported adverse events (AEs)

  At 1, 3, and 12 months post-treatment

• Incidence of patient-reported adverse events

  At 1, 3, and 12 months post-treatment

Study Arms (1)

Treatment (radiation therapy)

EXPERIMENTAL

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.

Procedure: Computed Tomography; Procedure: Nasopharyngeal Laryngoscopy; Procedure: Positron Emission Tomography; Other: Questionnaire Administration; Radiation: Radiation Therapy

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (radiation therapy)

Nasopharyngeal Laryngoscopy PROCEDURE

Undergo nasopharyngolaryngoscopy

Treatment (radiation therapy)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (radiation therapy)

Questionnaire Administration OTHER

Ancillary studies

Treatment (radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (radiation therapy)

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically confirmed HPV-related OPSCC, confirmed by HPV in-situ hybridization
• Patients must not have received prior treatment (i.e., no induction chemotherapy)
• Patients must have evaluable disease (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\]1.1 response criteria)
• Patients must be age \>= 18 years
• Patients must have American Joint Committee on Cancer (AJCC) 8th 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)
• Patient must receive a staging PET scan prior to registration on study
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patients may be planned to undergo radiation therapy (RT) alone or RT with concurrent chemotherapy, with chemotherapy managed at the discretion of the treating medical oncologist per standard of care
• 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)
• 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
• Patients must have the ability to understand and the willingness to sign a written informed consent document prior to registration

You may not qualify if:

• Patients with cT4, cN3, or cM1 disease by AJCC 8th edition
• Patients who have had prior RT to the head/neck region that would result in overlap of RT fields
• Patients who have had prior major surgery to the head/neck region that could disrupt lymphatic flow
• 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

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Magnetic Resonance Spectroscopy; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Therapeutics; Physical Phenomena

Study Officials

• Laila A Gharzai

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will undergo standard of care treatment with definitive radiotherapy, to a dose of 70 Gy to gross tumor (per standard of care) and 30 Gy to the elective neck.

Study Record Dates

• First Submitted: September 10, 2025
• First Posted: September 17, 2025
• Study Start: March 20, 2026
• Primary Completion (Estimated): March 20, 2030
• Study Completion (Estimated): March 20, 2031
• Last Updated: September 17, 2025

Record last verified: 2025-09

Locations

US (1)