Treatment De-Escalation for Favorable Prognosis Human Papilloma Virus (HPV) or p16-Positive Oropharyngeal Cancer Receiving Definitive Radiotherapy (Lombardi197)

A Phase II Study of Treatment De-Escalation for Favorable Prognosis, Stage I-II Human Papilloma Virus (HPV) or p16-Positive Oropharyngeal Cancer Receiving Definitive Radiotherapy

The current standard treatment option for Human Papillomavirus (HPV) or p16-positive oropharyngeal cancer is full-dose radiation combined with chemotherapy. Results with chemotherapy combined with full-dose radiation therapy leads to high rates of cure; this has called into question whether therapy can be decreased in intensity since both chemotherapy and radiation have long-term side effects. One approach to decrease intensity of treatment is to give radiation alone (excluding chemotherapy) and to decrease radiation therapy dose. The investigator believes that omitting chemotherapy and decreasing radiation dose both to tumor and the regions of the head and neck at highest risk of potential spread, may have no significant impact on the cancer recurring while potentially leading to fewer long-term side effects.

Study Overview

• Status: Recruiting
• Conditions: HPV; Tonsil Cancer; Oropharyngeal Cancers; Base of Tongue Cancer
• Intervention / Treatment: Radiation: Radiation

Detailed Description

This study aims to estimate the efficacy of radiation dose de-escalation while omitting chemotherapy for favorable prognosis HPV or p16-positive oropharyngeal cancer patients receiving definitive radiation therapy, where efficacy is measured by 2-year progression free survival (PFS) rate after treatment de-escalation for low-risk HPV+ oropharyngeal squamous cell carcinoma. This study also aims to determine quality of life parameters, complete clinical and radiographic response, as well as local, regional and distant metastasis control as well as overall survival.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicole Swanson; Email: ns1209@georgetown.edu
• Study Contact Backup: Name: Peter H Ahn, MD; Phone Number: 202-444-6385; Email: peter.h.ahn@gunet.georgetown.edu

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • MedStar Georgetown University Hospital
      • Contact: Peter H Ahn, MD; Phone Number: 202-444-6385; Email: peter.h.ahn@gunet.georgetown.edu
      • Principal Investigator: Peter H Ahn, MD
  • Maryland
    • Clinton, Maryland, United States, 20735
      • Recruiting
      • MedStar Southern Maryland Hospital Center
      • Contact: Peter H Ahn, MD; Phone Number: 202-444-6385; Email: peter.h.ahn@gunet.georgetown.edu
      • Principal Investigator: Peter H Ahn, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients must be ≥ 18 years of age on the day of signing informed consent.
• Patients must have a diagnosis of p16+ and/or HPV+ squamous cell carcinoma of the oropharynx (including base of tongue, glossotonsilar sulcus, tonsil, soft palate, vallecula, and/or posterior oropharyngeal wall).
• clinical stage stage I-II (T1-2 N1 M0, or T3 N0-1 M0 ) (AJCC 8th ed.) SCCA of the oropharynx that would mandate definitive chemoradiation as current standard of care when standard radiation fractionation is applied. Debulking of the disease by resecting the exophytic portion of the tumor for biopsy/sample or symptom alleviation will be permitted, as long as gross unresected tumor is left behind.
• Subjects must agree to biopsy of areas that are FDG-avid on PET-CT scan 3-4 months after treatment.
• Patients must have Karnofsky Performance Status (KPS) ≥ 60 within 8 weeks prior to registration
• Patients must have had a neutrophil:lymphocyte ratio ≤ 5 within 8 weeks of registration.
• Patient must have had a hemoglobin count ≥ 10 within 8 weeks of registration. The patient may receive transfusion to reach this goal.
• Patients must be a current non-smoker (at least 6 months) with ≤ 15 pack-year smoking history
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Patients with gross involvement of level 4 lymph node level
• Endophytic T3 disease, as clinically determined by the principal investigator.
• Patients with any single lymph node > 4cm (multiple lymph nodes including nodal conglomerates that in sum measure >4cm is allowed)
• Patients with nodal disease clinically fixed to or radiographically invading adjacent neck musculature any single lymph node > 4cm (multiple lymph nodes including nodal conglomerates that in sum measure >4cm is allowed)
• Prior history of malignancy diagnosed within 2 years prior to registration, except for nonmelanomatous skin cancer that has completed treatment and the patient is deemed as being disease-free, or Gleason 6 prostate cancer undergoing active surveillance.
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

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: Radiation only; Radiation therapy only to a dose of 66Gy to gross disease	Radiation: Radiation; Radiation only to 66Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression Free Survival- 2-year progression free survival, as determined by standard of care physical examination and standard of care surveillance imaging.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Control of disease (LC) rate	Number of patient with local control at 2 years, as determined by standard of care physical examination and/or standard of care surveillance imaging.	2 years
Regional Control of diseaes (RC) rate	Number of patient with regional control at 2 years, as determined by standard of care physical examination and/or standard of care surveillance imaging.	2 years
Distant Metastasis-Free Survival (DMFS) rate	Distant Metastasis-Free Survival as determined by standard of care physical examination and standard of care surveillance imaging at 2 years.	2 years
Overall Survival (OS)	Defined a time from start of treatment until end of study or death.	2 years
Quality of life (QOL) Core Questionnaire	Estimate differences in quality of life (QOL) parameters between patients treated with intensity-modulated photon radiation therapy versus proton beam radiation therapy (RT) related to radiation dose to organs at risk (OAR). QOL will be measured by validated questionnaires relating to patient related outcomes. Completed at baseline, and then at 1-2 weeks, 3 months, 6, 12, 18 and 24 months after completion of RT. EORTC QLQ Core Questionnaire (EORTC QLQ-C30), scale 0-100 with 100 being the best outcome.	2 years
Quality of life (QOL) Head and Neck Cancer	Estimate differences in quality of life (QOL) parameters between patients treated with intensity-modulated photon radiation therapy versus proton beam radiation therapy (RT) related to radiation dose to organs at risk (OAR). QOL will be measured by validated questionnaires relating to patient related outcomes. Completed at baseline, and then at 1-2 weeks, 3 months, 6, 12, 18 and 24 months after completion of RT. Head and Neck Cancer (QLQ-H&N35), scale 0-100 with 100 being the best outcome.	2 years
Rate of percutaneous endocsopic gastrostomy (PEG) tube placement	Number of patients with PEG tube placement and presence of PEG tube at 1 year in patients who are treated with de-escalated definitive radiotherapy.	1 year
Rate of neck dissection	Number of subjects with neck dissection within 12 weeks of treatment completion due to equivocal examination findings, even if the neck dissection shows no residual disease.	12 weeks post treatment completion

Collaborators and Investigators

• Sponsor: Georgetown University
• Investigators: Principal Investigator: Peter Ahn, MD, Georgetown University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 3, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): March 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

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; Tonsillar Neoplasms; Physical Phenomena; Radiation
• Other Study ID Numbers: STUDY00000197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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