Adaptive De-intensified Radiotherapy Using Circulating Tumor DNA in HPV- Associated Oropharyngeal Cancer
March 20, 2026 updated by: Dukagjin Blakaj, Ohio State University Comprehensive Cancer Center
A Pilot Study of Adaptive De-Intensified Radiotherapy Using Circulating Tumor DNA in HPV- Associated Oropharyngeal Cancer
This phase II trial studies how well using circulating tumor deoxyribonucleic acid (DNA) to guide lower dose radiation therapy works in treating patients with human papillomavirus infection (HPV)-associated oropharyngeal cancer.
Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors.
Recently, a blood test has been developed to detect the human papillomavirus in the blood and determine how many viral particles are present.
Researchers want to compare any good and bad effects of using the lower dose radiation therapy with chemotherapy compared to the usual standard of care dose chemotherapy in patients who clear the human papillomavirus particles from their blood.
Study Overview
Status
Status
Recruiting
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. To estimate the 3-month post-treatment positron emission tomography (PET) response rate in patients who have a favorable tumor tissue modified viral (TTMV) tumor profile (defined as >= 200 copies/mL and reduced to > 95% of this value by week 4).
SECONDARY OBJECTIVES:
I. To assess 2-year progression free survival and toxicity in the reduced dose chemo-radiation arm.
II. To determine acute and late toxicity as measured by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0).
III. To compare changes in the MD Anderson Dysphagia Inventory (MDADI) of reduced dose radiation to the current standard of care (69.96 Gy).
IV. To determine whether integration of HPV into the host genome is associated with circulating TTMV clearance profiles during chemoradiation (CRT).
OUTLINE:
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin intravenously (IV) weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4, and then are assigned to 1 of 2 arms based on the results.
ARM I: Patients with reduced > 95% of TTMV undergo external beam radiotherapy once daily (QD)5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients undergo PET/computed tomography (CT) scan throughout the trial. Patients also undergo blood sample collection during screening and throughout the trial.
ARM II: Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. Patients undergo PET/CT scan throughout the trial. Patients also undergo blood sample collection during screening and throughout the trial.
After completion of study treatment, patients are followed every 3 months for up to 24 months.
Study Type
Study Type
Interventional
Enrollment (Estimated)
Enrollment
45
Phase
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Recruiting
- Ohio State University Comprehensive Cancer Center
-
Principal Investigator:
- Sujith Baliga
-
Contact:
- Sujith Baliga
- Phone Number: 614-293-5066
- Email: Sujith.baliga@osumc.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Pathologically confirmed diagnosis of squamous cell carcinoma of the oropharynx (unknown primary, base of tongue, tonsil, oropharyngeal walls, soft palate). Cytologic or fine needle aspiration (FNA) confirmation is sufficient if a biopsy of the primary tumor is not feasible
- P16 positive immunohistochemical staining. FNA may be used as the sole diagnostic tissue. If staining was done at an outside hospital, central review by the Ohio State University (OSU) department of pathology must occur prior to trial enrollment
- Clinical stage T0, N1-N2, T1-2, N1-N2, T3-T4, N0-2 (American Joint Committee on Cancer [AJCC] 8th edition) including no evidence of distant metastases based on general history, imaging, physical examination, and examination with laryngopharyngoscopy
- Clinical or radiographic evidence of measurable disease at the primary site or lymph nodes. Simple tonsillectomy or excision of primary without removal of nodal disease is permitted, as is excision of gross nodes but with intact primary site
- Fludeoxyglucose F-18 (FDG) PET/CT from the base of skull to the mid-thigh is mandatory and patients cannot be enrolled without a pretreatment PET/CT. PET/CT must be completed prior to enrollment
- Pretreatment tumor tissue modified HPV virus (TTMV-HPV) particles present in plasma cell free DNA value of >= 200 copies/mL at baseline
- Patients must provide their smoking history prior to enrollment. Patients must have =< 10 pack years of smoking. The number of pack years will be calculated using the following formula: Frequency of smoking (cigarettes/day) x duration of cigarette smoking (years)/20
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Age >= 18
- Absolute neutrophil count: ≥ 1500/mcL (within 14 days prior to registration)
- Platelets: >= 100,000/mcL (within 14 days prior to registration)
- Hemoglobin >= 8.0 g/dL (use of transfusion or other intervention to achieve this is acceptable) (within 14 days prior to registration)
- Total bilirubin >= 1.5 x institutional upper limit of normal (within 14 days prior to registration)
- Aspartate transaminase (AST) or alanine transaminase (ALT) >= 3.0 x institutional upper limit of normal (within 14 days prior to registration)
- Serum creatinine =< 1.5 x institutional upper limit of normal or creatinine clearance >= 50 mL/min (Cockcroft-Gault Formula) (within 14 days prior to registration)
- Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
- Patients with known positive hepatitis B surface antigen indicating acute or chronic infection would make patient ineligible unless viral load becomes undetectable on suppressive therapy
- Patients with history of hepatitis C virus must have been treated and cured
- For women of childbearing potential, negative serum or urine pregnancy test within 14 days of registration
- Patient or legally authorized representative must provide study specific informed consent prior to study entry
Exclusion Criteria:
- Recurrent disease
- Clinical or radiographic evidence of metastatic disease or adenopathy below the clavicles
- Cancers from an oral cavity site, even if p16 positive
- Patients with simultaneous primary cancers or separate bilateral primary tumors will be excluded, except for patients with bilateral tonsil cancers
- Prior invasive malignancy (except non-melanoma skin cancer) unless disease free for a minimum of 3 years
- Prior systemic chemotherapy or immunotherapy
- Prior radiotherapy that would result in overlap of radiation fields
- Severe active co-morbidity defined as: Unstable angina or congestive heart failure requiring hospitalization in the last 6 months. Condition requiring systemic treatment with steroids or immunosuppressive medications within 14 days of registration
- Patients with active autoimmune disease requiring systemic treatment (disease modifying agents, corticosteroids, or immunosuppressive drugs
- Patients who are pregnant, nursing, or expected to conceive or father children
- Patients who are allergic to cisplatin, carboplatin, or paclitaxel
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Number of Arms
2
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: Arm I (reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4. Patients with reduced > 95% of TTMV undergo external beam radiotherapy QD 5 days a week for 5 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 5 weeks. Patients also undergo blood sample collection during screening and throughout the trial. |
Given IV
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Undergo PET/CT
Other Names:
Undergo PET/CT
Other Names:
Undergo external beam radiotherapy
Other Names:
|
|
Active Comparator: Arm II (not reduced > 95% of TTMV, external beam radiotherapy)
Patients undergo external beam radiotherapy daily for 5 days a week for 4 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 4 weeks. Patients undergo blood sample collection for circulating tumor DNA testing at week 4. Patients without reduced > 95% of TTMV undergo external beam radiotherapy daily for 5 days a week for 7 weeks. Patients also receive cisplatin IV weekly or every 3 weeks or carboplatin/paclitaxel IV weekly at the discretion of treating physician for 7 weeks. . Patients also undergo blood sample collection during screening and throughout the trial. |
Given IV
Other Names:
Ancillary studies
Given IV
Other Names:
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Undergo PET/CT
Other Names:
Undergo PET/CT
Other Names:
Undergo external beam radiotherapy
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Positron emission tomography complete response
Time Frame: At 3 months
|
Will be evaluated using the Hopkins Criteria which predicts Overall Survival (OS) and Progression-free survival (PFS) in patients with HPV positive oropharyngeal cancers.
Separate scores are given for the primary tumor, right neck, and left neck.
The activity in the internal jugular vein (IJV) is taken as background blood pool for reference.
A score of 1 is consistent with a complete metabolic response, a score of 2 is associated with likely complete metabolic response, a score of 3 is likely inflammatory changes, and a score of 4 is considered likely residual tumor.
The overall assessment is denoted by the overall score, which is the highest score among the scores for the primary tumor and right and left neck.
|
At 3 months
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of adverse events
Time Frame: Up to 1 year
|
The treating physician will evaluate all adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Any adverse event which changes CTCAE grade over the course of a given episode will have each change of grade recorded in the electronic medical record.
|
Up to 1 year
|
|
Quality of life (QOL)
Time Frame: Up to 1 year
|
Will be measured by the MD Anderson Dysphagia Inventory (MDADI) global QOL score.
The MDADI is a 20-item self-administered patient reported dysphagia assessment instrument and incorporates global, functional, emotion, and physical subscales.
Two overall scores are obtained which include the global and composite scores.
The global score is from a single item and the composite score summarizes the remaining 19 items as a weighted average of the physical, emotional, and functional subscales.
The scores range from 0 (extremely low functioning) to 100 (high functioning).
|
Up to 1 year
|
|
Progression free survival
Time Frame: At 2 years
|
Will be will be analyzed using Kaplan Meier methods.
|
At 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Sponsor
Investigators
Investigators
- Principal Investigator: Sujith Baliga, Ohio State University Comprehensive Cancer Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
Study Start
March 21, 2024
Primary Completion (Estimated)
Primary Completion
December 31, 2026
Study Completion (Estimated)
Study Completion
December 31, 2026
Study Registration Dates
First Submitted
First Submitted
March 14, 2024
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
March 14, 2024
First Posted (Actual)
First Posted
March 21, 2024
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
March 24, 2026
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
March 20, 2026
Last Verified
Last Verified
March 1, 2026
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Stomatognathic Diseases
- Neoplasms by Site
- Neoplasms
- Neoplasms by Histologic Type
- Head and Neck Neoplasms
- Neoplasms, Glandular and Epithelial
- Carcinoma
- Otorhinolaryngologic Diseases
- Pharyngeal Neoplasms
- Otorhinolaryngologic Neoplasms
- Pharyngeal Diseases
- Carcinoma, Squamous Cell
- Squamous Cell Carcinoma of Head and Neck
- Oropharyngeal Neoplasms
- Organic Chemicals
- Investigative Techniques
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Hydrocarbons
- Cycloparaffins
- Hydrocarbons, Alicyclic
- Hydrocarbons, Cyclic
- Terpenes
- Physical Phenomena
- Inorganic Chemicals
- Chlorine Compounds
- Nitrogen Compounds
- Coordination Complexes
- Taxoids
- Cyclodecanes
- Diterpenes
- Elements
- Metals
- Organizations
- Health Care Economics and Organizations
- Chemistry Techniques, Analytical
- Spectrum Analysis
- Metals, Heavy
- Platinum Compounds
- Transition Elements
- Economics
- Carboplatin
- Paclitaxel
- Cisplatin
- 1,2-diaminocyclohexaneplatinum II citrate
- Radiation
- Congresses as Topic
- Specimen Handling
- Magnetic Resonance Spectroscopy
- Platinum
- Taxes
Other Study ID Numbers
Other Study ID Numbers
- OSU-23083
- NCI-2024-00904 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
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
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
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