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

NCT06323460 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-23083NCI-2024-00904
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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 II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Oropharyngeal Squamous Cell Carcinoma; Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Positron emission tomography complete response

  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 Outcomes (3)

• Progression free survival

  At 2 years

• Incidence of adverse events

  Up to 1 year

• Quality of life (QOL)

  Up to 1 year

Study Arms (2)

Arm I (reduced > 95% of TTMV, external beam radiotherapy)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Cisplatin; Procedure: Computed Tomography; Radiation: External Beam Radiation Therapy; Drug: Paclitaxel; Procedure: Positron Emission Tomography; Other: Questionnaire Administration

Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

ACTIVE COMPARATOR

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.

Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Cisplatin; Procedure: Computed Tomography; Radiation: External Beam Radiation Therapy; Drug: Paclitaxel; Procedure: Positron Emission Tomography; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (reduced > 95% of TTMV, external beam radiotherapy); Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (reduced > 95% of TTMV, external beam radiotherapy); Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm I (reduced > 95% of TTMV, external beam radiotherapy); Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Arm I (reduced > 95% of TTMV, external beam radiotherapy); Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

External Beam Radiation Therapy RADIATION

Undergo external beam radiotherapy

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Arm I (reduced > 95% of TTMV, external beam radiotherapy); Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (reduced > 95% of TTMV, external beam radiotherapy); Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Arm I (reduced > 95% of TTMV, external beam radiotherapy); Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

Questionnaire Administration OTHER

Ancillary studies

Arm I (reduced > 95% of TTMV, external beam radiotherapy); Arm II (not reduced > 95% of TTMV, external beam radiotherapy)

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Oropharyngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Specimen Handling; Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Congresses as Topic; Radiation; Paclitaxel; Taxes; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Organizations; Health Care Economics and Organizations; Physical Phenomena; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Sujith Baliga

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 14, 2024
• First Posted: March 21, 2024
• Study Start: March 21, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)