Clinical trial NCT06902623: Treatment De-Escalation for Favorable Prognosis Human Papilloma Virus (HPV) or p16-Positive Oropharyngeal Cancer Receiving Definitive Radiotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Oropharyngeal Cancers
HPV
Tonsil Cancer
Base of Tongue Cancer
Lead sponsor: Georgetown University
Sponsor class: OTHER
First posted: 2025-03-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Local Control of disease (LC) rate
timeFrame: 2 years
measure: Regional Control of diseaes (RC) rate
timeFrame: 2 years
measure: Distant Metastasis-Free Survival (DMFS) rate
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Quality of life (QOL) Core Questionnaire
timeFrame: 2 years
measure: Quality of life (QOL) Head and Neck Cancer
timeFrame: 2 years
measure: Rate of percutaneous endocsopic gastrostomy (PEG) tube placement
timeFrame: 1 year
measure: Rate of neck dissection
timeFrame: 12 weeks post treatment completion
Other outcomes:
Locations:
city: Washington
country: United States
facility: Medstar Georgetown University Hospital
state: District of Columbia
city: Clinton
country: United States
facility: Medstar Southern Maryland Hospital Center
state: Maryland
Study officials:
affiliation: Georgetown University
name: Peter Ahn, MD
role: PRINCIPAL_INVESTIGATOR
References: