Omission of Postoperative Radiation in HPV-Associated Oropharyngeal Cancer Using ctHPVDNA Surveillance (OPERATION)

NCT07513389 | Recruiting Phase 2 DMC

• 1 other identifier: 104270
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm Phase II trial evaluates whether omission of postoperative radiotherapy is feasible and oncologically safe in select patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC). Eligible patients undergo transoral robotic surgery (TORS) and are observed without adjuvant radiation if they demonstrate low or intermediate pathological risk features and have negative circulating tumor HPV DNA (ctHPVDNA) two weeks post-operatively. Patients are followed with standard clinical surveillance combined with serial ctHPVDNA testing (NavDx®) to facilitate early detection of recurrence and prompt salvage therapy as needed.

Conditions

Squamous Cell Carcinoma; Human Papilloma Virus (HPV); Oropharyngeal Squamous Cell Carcinoma (OPSCC)

Outcome Measures

Primary Outcomes (1)

• Local-Regional Control

  Proportion of participants without local or regional recurrence above the clavicles at 2 years following definitive surgery, including participants who recur but are successfully salvaged with radiation or chemotherapy during the 2-year postoperative period.

  2 years post-surgery

Secondary Outcomes (7)

• Progression-Free Survival (PFS)

  2 years after definitive surgery

• Distant Metastasis-Free Survival (DMFS)

  2 years after definitive surgery

• Overall Survival (OS)

  2 years after definitive surgery

• Swallowing Function (Functional Oral Intake Scale - FOIS)

  Baseline through 24 months post-surgery

• Swallowing-Related Symptoms (Eating Assessment Tool-10 - EAT-10)

  Baseline through 24 months post-surgery

Study Arms (1)

Active Surveillance With ctHPVDNA After Surgery

EXPERIMENTAL

Participants with negative postoperative ctHPVDNA are observed without adjuvant radiation and followed with routine clinical surveillance and serial ctHPVDNA testing.

Other: Active Surveillance With ctHPVDNA (NavDx®)

Interventions

Active Surveillance With ctHPVDNA (NavDx®) OTHER

Active surveillance without postoperative radiation using routine clinical follow-up and serial ctHPVDNA testing to detect recurrence.

Active Surveillance With ctHPVDNA After Surgery

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, ≥ 18 years of age (no upper age limit).
• Biopsy proven squamous cell carcinoma.
• p16 positive (diffuse ≥ 70% tumor cell expression, with at least moderate (2/3+ staining intensity).
• NavDx positive, HPV16 TTMV only.
• AJCC 8th edition cT0-2 N1 M0.
• Well lateralized tonsil (\>1 cm from midline, tonsil, base of tongue, glossotonsillar sulcus primary tumors.
• ≤ 2 lymph nodes, each ≤ 3cm, -OR- 1 lymph node \>3 but \< 6 cm.
• ≤10 pack-years of cigarette smoking or no cigarette smoking for ≥ 5 years (regardless of pack years).
• Anatomically (e.g. adequate exposure) and physically amenable to TORS per the judgement of the operating surgeon.
• Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to surgery; at a minimum CT imaging of the chest. PET/CT is acceptable.
• ECOG Performance Status 0-1.
• CBC with differential obtained within 8 weeks prior to surgery, with adequate bone marrow function defined as follows:
• Platelets ≥ 100,000 cells/mm3

You may not qualify if:

• Prior history of surgery to the head and neck that in the opinion of the investigators would modify prognostic significance of pathology results.
• Prior history of radiation therapy to the head and neck, with the exception of skin cancer treated with a small (≤ 9cm3) field with 6 - 9 MeV electron beam or 50 - 250 kVp photon beam.
• Prior history within 5 years of cancer with the exception of:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin, stage 1-2
• Prostate cancer without distant metastases (stage M0)
• Thyroid cancer without distant metastases (stage M0)
• Prior history of squamous cell carcinoma of a mucosal site in the head or neck treated with surgery alone.
• Currently taking Disease Modifying Rheumatoid Drugs (DMRDs) or immunosuppressive medication, for example as for organ transplant or multiple sclerosis.
• Current smoker or tobacco user.
• Severe, active co-morbidity, defined as one or more of the following:
• Unstable angina and/or congestive heart failure requiring inpatient hospitalization within the last 6 months.
• Transmural myocardial infarction within the last 6 months.
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration.
• Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Bhishamjit Chera, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

HCC Clinical Trials Office

CONTACT

843-792-9321; hcc-clinical-trials@musc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 7, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2030
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)