Squamous Cell CarcinomaPhase 2NCT07513389
Omission of Postoperative Radiation in HPV-Associated Oropharyngeal Cancer Using ctHPVDNA Surveillance (OPERATION)
A Phase 2 study testing Active Surveillance With ctHPVDNA (NavDx®) in people with Squamous Cell Carcinoma and Human Papilloma Virus (HPV), run by Medical University of South Carolina at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Carcinoma, Human Papilloma Virus (HPV), Oropharyngeal Squamous Cell Carcinoma (OPSCC)
- What is being tested?
- Active Surveillance With ctHPVDNA (NavDx®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Aug 2026to 1 Jul 2034
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Hemoglobin ≥ 9.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dl is acceptable. Transfusion must be completed within 2 to 4 weeks prior to enrollment.)
- Adequate renal and hepatic function within 8 weeks prior to surgery, defined as follows:
- Serum creatinine < 2.0 mg/dl.
- Total bilirubin ≤ 1.5 x the institutional ULN.
- Negative pregnancy test within 2 weeks prior to surgery for women of childbearing potential.
- Eligible for platinum chemotherapy. Chemotherapy drugs allowed: cisplatin, carboplatin/paclitaxel, carboplatin/abraxane, per treating physician (cisplatin preferred, 2nd preference carboplatin/paclitaxel or carboplatin/abraxane).
- For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional year after surgery per MD discretion. Acceptable forms of birth control include hormonal contraceptives (such as birth control pills, skin patch, vaginal ring, injection, and/or implant), intrauterine devices (IUDs), and barrier devices (such as condoms, diaphragm, cervical cap, and sponge).
Who cannot join
- 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)
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- 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
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
- --- Note, however, coagulation parameters are not required for entry into this protocol.
- Evidence of active systemic lupus or scleroderma.
- Psoriatic arthritis.
- Known HIV positivity. HIV positive patients are known to have worse clinical outcomes especially for local, regional, and distant cancer control. This poorer prognosis is thought to be secondary to a compromised immune system. Thus, de-intensification of radiation and chemotherapy is not justifiable in this population.
- -- Note: HIV testing at the time of enrollment is not required.
- Subjects of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for the immediate post-op period (1-2 weeks). Females will be determined to be not of child-bearing potential with a history of hysterectomy or with postmenopausal status of >12 months.
- Pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting one month prior to screening and for one year after surgery per MD discretion.
- Prisoners or subjects who are involuntarily incarcerated, or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
HCC Clinical Trials Office, 843-792-9321, hcc-clinical-trials@musc.edu
About this study
Official title: Omission of Immediate Postoperative Radiation in Patients With Intermediate Pathological Risk Features and Negative Two-Week Post-Operative ctHPVDNA (OPERATION Trial)
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)
- Being tested
- Active Surveillance With ctHPVDNA (NavDx®)
- Medical subject headings
- Carcinoma, Squamous Cell, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Surveillance With ctHPVDNA (NavDx®)Other
Active surveillance without postoperative radiation using routine clinical follow-up and serial ctHPVDNA testing to detect recurrence.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Active Surveillance With ctHPVDNA (NavDx®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years post-surgery
Secondary outcomes (7)
Progression-Free Survival (PFS)
Time from surgery to disease progression or death from any cause.
Measured: 2 years after definitive surgery
Distant Metastasis-Free Survival (DMFS)
Time from surgery to development of distant metastatic disease or death.
Measured: 2 years after definitive surgery
Overall Survival (OS)
Time from surgery to death from any cause.
Measured: 2 years after definitive surgery
Swallowing Function (Functional Oral Intake Scale - FOIS)
Change in swallowing function measured using the Functional Oral Intake Scale (FOIS).
Measured: Baseline through 24 months post-surgery
Swallowing-Related Symptoms (Eating Assessment Tool-10 - EAT-10)
Change in patient-reported swallowing symptoms measured using the EAT-10 questionnaire.
Measured: Baseline through 24 months post-surgery
ctHPVDNA Detection of Recurrence
Proportion of recurrences first detected by ctHPVDNA positivity prior to clinical or radiographic recurrence.
Measured: Up to 5 years
Time From ctHPVDNA Positivity to Clinical Detection
Number of days between initial ctHPVDNA positivity and clinical or radiographic confirmation of recurrence.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2026
- Study start12 Aug 2026
- Primary completion31 Oct 2031 (estimated)
- Study completion1 Jul 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bhishamjit Chera, Medical University of South Carolina
- Investigators
- Bhishamjit Chera, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07513389
- Sponsor's protocol ID
- 104270
- Status last verified
- Jun 2026
- First submitted
- 1 Apr 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No