Selective Adjuvant Therapy for HPV-mediated Oropharynx SCCs Based on Residual Circulating Tumor DNA Levels (SAVAL)

NCT06088381 | Recruiting Phase 2 DMC

• 1 other identifier: HP-00106914
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 5

Brief Summary

Patients with human papillomavirus (HPV)-related oropharyngeal cancer generally have favorable outcomes and how well they do depends on the specific details about the patient and their cancer. How well they do isn't as related to the kinds of treatment they get. However, there are significant side effects for the various types of treatments they may get. Because these patients generally have favorable outcomes no matter the kind of treatment, reducing side effects should be a priority when choosing their treatment. The goal of this clinical research study is to evaluate whether a new blood test called a Circulating Tumor DNA test (ctDNA test) can decrease the number of people that require radiation after surgery. This blood test is often elevated in people when they are diagnosed with head and neck cancer. There are studies that show that cancer most often returns when this blood test is positive after treatment. This study will test patients' blood before and after surgery. In cases where the test is negative after surgery, people on the study will not receive radiation unless they are considered high risk based on surgery findings. The hope is that radiation and its potential side effects can be limited to only people that need the treatment.

Conditions

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Oropharynx Cancer; Oropharynx Squamous Cell Carcinoma; HPV Positive Oropharyngeal Squamous Cell Carcinoma

Keywords

Transoral Robotic Surgery (TORS); Head and Neck Cancer; Oropharynx Cancer; HPV p16 Oropharynx Cancer; Proton Therapy; Photon Therapy

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Percent PFS at 2 year post last treatment inclusive of patients undergoing salvage treatment for LRR.

  2 year post last treatment

Secondary Outcomes (9)

• Rate of Recurrence

  1 year post TORS

• Rate of Salvage

  2 years post TORS

• Locoregional recurrence (LRR)

  2 year post last treatment

• Overall Survival (OS)

  2 year post last treatment

• Number of participants free from distant metastases

  2 year post last treatment

Study Arms (1)

Intermediate Risk Experimental Observation

EXPERIMENTAL

Requires the following criteria: 1. Pathological T1-3 N1-2 with negative surgical margins 2. Absent or microscopic extracapsular extension(ECE) (≤1mm) 3. ctDNA positive pre-operatively and negative post-operatively This group will undergo observation on the experimental arm of the study. They will be monitored for toxicity, Quality of Life (QoL) and outcomes evaluation. Suspected locoregional recurrence (LRR) based on physical examination, imaging or increasing ctDNA will undergo completion of workup at the discretion of the University of Maryland Head and Neck tumor board. LRR will be offered salvage treatment based on recommendations from multi-disciplinary discussion. Salvage therapy could include surgical resection (with or without adjuvant treatment), and definitive RT (with or without chemotherapy).

Other: Experimental Observation; Other: Observation per Standard of Care; Radiation: Adjuvant Treatment per Standard of Care; Diagnostic Test: Circulating Tumor DNA test (ctDNA test)

Interventions

Experimental Observation OTHER

Patients on the experimental arm will be under observation only.

Intermediate Risk Experimental Observation

Observation per Standard of Care OTHER

The low-risk group of patients will be observed per standard of care.

Intermediate Risk Experimental Observation

Adjuvant Treatment per Standard of Care RADIATION

The high-risk group of patients will receive adjuvant treatment per standard of care (Radiation with or without chemotherapy)

Intermediate Risk Experimental Observation

Circulating Tumor DNA test (ctDNA test) DIAGNOSTIC_TEST

Blood test for diagnostic and surveillance purposes measuring expression of Cell free HPV tumor DNA (ctDNA) in the blood. Patients will undergo ctDNA within 90 days pre-transoral robotic surgery(TORS), 2-14 days post TORS, then every 3 months (except for at 21 months) for 2 year post completion of initial therapy or salvage therapy.

Intermediate Risk Experimental Observation

Eligibility Criteria

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

You may qualify if:

• Is there pathologically (histologically or cytologically) proven diagnosis of p16+ squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx or p16+ squamous cell carcinoma unknown primary? Note: specimen from cervical lymph nodes with a well-defined primary site documented clinically or radiologically is acceptable; in patients with carcinoma of unknown primary this will be sufficient for pathologic confirmation without a clinically or radiographically defined primary site.
• Does the patient have clinical stage T0-3, N0-N1, and M0 disease (AJCC 8th edition) as defined by physical examination and appropriate imaging (PET/CT preferred, CT neck with IV contrast with CT chest without contrast as recommended alternative to PET/CT) with imaging within 60 days of enrollment?
• Has the patient completed a ctDNA evaluation with results demonstrating positive ctDNA levels prior to surgery either in blood or on biopsy tissue?
• Upon multi-disciplinary review, is the patient a candidate for TORS based on evaluation by ear, nose, throat (ENT) and review at multi-disciplinary tumor board?
• Was a general history and physical examination performed by a radiation oncologist, medical oncologist, or head and neck surgeon within 60 days prior to registration?
• Was the patient's Zubrod Performance Status 0-1 within 30 days prior to registration?
• Is the patient ≥ 18 years of age?
• If a woman of child-bearing potential or sexually active male, is the patient willing to use effective contraception throughout their participation in the treatment phase of the study and at least 180 days following the last study treatment.
• Did the patient provide study specific informed consent prior to study entry, including consent for mandatory submission of tissue for required p16 review?

You may not qualify if:

• Does the patient have cancer considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx?
• Does the patient have distant metastasis?
• Does the patient have prior invasive malignancy (except non-melanomatous skin cancer and low/intermediate risk prostate cancer) unless disease free for a minimum of 3 years?
• Did the patient have prior systemic chemotherapy for the study cancer (prior chemotherapy for a different cancer is allowable)?
• Did the patient have prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields?
• Did the patient have prior cancer related surgeries of the head and neck excluding superficial removal of cutaneous skin malignancies?
• Does the patient have any co-morbid condition or concern that may interfere with follow up per experimental arm?
• Does the patient have an active drug or alcohol dependency that in the opinion of the investigator would limit compliance with study requirements?
• Is the patient pregnant or nursing (an exception will be made for nursing patients that are not receiving chemotherapy)?

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (5)

Maryland Proton Treatment Center

Baltimore, Maryland, 21201, United States

RECRUITING

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

Upper Chesapeake Health

Bel Air, Maryland, 21014, United States

NOT YET RECRUITING

Central Maryland Radiation Oncology

Columbia, Maryland, 21044, United States

NOT YET RECRUITING

Baltimore Washington Medical Center

Glen Burnie, Maryland, 21061, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Jason K Molitoris, MD, PhD

  University of Maryland/Maryland Proton Treatment Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason K Molitoris, MD, PhD

CONTACT

410-328-6080; jmolitoris@umm.edu

Kelly Kitzmiller, MPH

CONTACT

410-369-5264; kelly.kitzmiller@umm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 28, 2023
• First Posted: October 18, 2023
• Study Start: March 7, 2024
• Primary Completion (Estimated): December 18, 2028
• Study Completion (Estimated): December 18, 2030
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (5)