Recruiting

Phase 2

Radiotherapy with ctDNAAdaptive De-intensified Radiotherapy Using Circulating Tumor DNA in HPV- Associated Oropharyngeal Cancer

Sponsor:

Ohio State University Comprehensive Cancer Center

Code:

NCT06323460

Conditions

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

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

Oropharyngeal Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Carboplatin

Cisplatin

Computed Tomography

External Beam Radiation Therapy

Study Details

Brief summary:

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.

Conditions

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

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

Oropharyngeal Squamous Cell Carcinoma

Study ID

NCT06323460

Start date

Mar 21, 2024

Status verified date

Mar, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

45 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

Interventions

Biospecimen Collection

Undergo blood sample collection

Carboplatin

Given IV

Cisplatin

Given IV

Computed Tomography

Undergo PET/CT

External Beam Radiation Therapy

Undergo external beam radiotherapy

Paclitaxel

Given IV

Positron Emission Tomography

Undergo PET/CT

Questionnaire Administration

Ancillary studies

Primary outcome measure

Positron emission tomography complete response [ Time Frame: At 3 months ]

Central Contacts and Locations

Locations

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Sujith Baliga

614-293-5066 Sujith.baliga@osumc.edu

Principal Investigator:

Sujith Baliga

More Information

Sponsor

Ohio State University Comprehensive Cancer Center

Last update posted

Mar 24, 2026

Last verified

Mar, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Ohio State University Comprehensive Cancer Center on 2026-03-24.