Recruiting

ctHPVDNActHPVDNA in HPV Positive Squamous Cell Carcinoma of the Oropharynx

Sponsor:

Indiana University

Code:

NCT06915038

Conditions

Squamous Cell Carcinoma of Oropharynx

HPV Positive Cancer

Throat Cancer

Tonsil Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

NavDx

Adjuvant Radiation 30 Gray

Adjuvant Radiation 40 Gray

Study Details

Brief summary:

This study is a prospective phase II trial, designed to assess the efficacy and feasibility of adjuvant treatment deintensification guided by ctHPVDNA levels for patients with HPV+OPSCC who undergo transoral surgery and neck dissection.

Conditions

Squamous Cell Carcinoma of Oropharynx

HPV Positive Cancer

Throat Cancer

Tonsil Cancer

Study ID

NCT06915038

Start date

Jun 11, 2025

Status verified date

Aug, 2026

Completion date

Dec, 2028

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Pre-Surgery

Subjects ≥ 18 years old at the time of informed consent.
Ability to provide written informed consent and HIPAA authorization.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Primary tumor of the oropharynx (palatine tonsil, tongue base, soft palate, lateral or posterior walls of oropharynx).
Histopathologically confirmed squamous cell carcinoma.
Detectable ctHPVDNA from blood samples collected prior to treatment.
Resectable and accessible tumor with high probability of achieving negative margins.
Smokers and non-smokers included.
Tumor stage (AJCC 8th edition): T1 or T2, and select T3 tumors that are mobile and do not invade the larynx.
Nodal stage (AJCC 8th edition): N0, N1 or N2.
HPV+ tumor, as determined by p16, in-situ hybridization, real-time polymerase chain reaction, or ctHPVDNA.

Post-Surgery

• Subjects with unknown primaries included if primary is definitively identified and resectable with negative margins or if the palatine and lingual tonsils are thoroughly resected and pathologically proven to be negative for a primary.

Exclusion Criteria:

Serious medical condition preventing general anesthesia for surgery.
History of previous head and neck radiation or previous head and neck cancer within 3 years.
Distant metastatic disease present.
Subjects with synchronous HPV+ oropharynx primaries
Prior invasive malignant disease within 3 years, with the exception of non-melanoma skin cancer and thyroid cancer, unless patient is deemed cured or disease free, in which case patient may be included in the study.
Lactating or pregnant women. Women of childbearing potential must have a negative pregnancy test on the day of surgery. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:

1. Has undergone a hysterectomy or bilateral oophorectomy; or
2. Has been naturally amenorrheic for at least 12 consecutive months.

Study Design

Enrollment

120 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Observation

Subjects with undetectable postoperative ctHPVDNA levels and either 4 or fewer nodes will have no further adjuvant treatment.

experimental: Adjuvant Radiation 30 Gray

Subjects with undetectable postoperative ctHPVDNA levels after surgery, negative margins, and five or more positive nodes; or confirmed extranodal extension (ENE) (greater than 2 mm) will undergo deintensified radiation treatment of 30 gray.

experimental: Adjuvant Radiation 40 Gray

Subjects with positive postoperative ctHPVDNA will undergo reimaging to evaluate for potentially operable disease, followed by appropriate surgery as indicated. If surgery is performed, repeat ctHPVDNA levels will be checked, and if then negative, subject will be placed in observation or 30 Gy of radiation depending on nodal status.

If repeat ctHPVDNA level is positive, or subject has no obvious operable disease then subject will undergo 40 Gy of radiation.

Interventions

NavDx

NavDx is a clinically validated blood test to detect circulating tumor HPV DNA (ctHPVDNA). In this study, ctHPVDNA results, in conjuction with specimen analysis, will be used to assign post-surgical adjuvant treatment.

Adjuvant Radiation 30 Gray

If undetectable postoperative ctHPVDNA levels and five or more positive nodes, or confirmed extranodal extension (ENE) (greater than 2 mm) deintensified radiation treatment of 30 gray.

Adjuvant Radiation 40 Gray

If detectable postoperative ctHPVDNA, then reimage to evaluate for potentially operable disease, followed by appropriate surgery as indicated. If surgery is performed, repeat ctHPVDNA levels will be checked, and if then negative, subject will be placed in observation if N0 or N1 disease, and 30 Gy of radiation if N2 disease on final pathologic staging. If repeat ctHPVDNA level is positive, or shows no obvious operable disease, then subject will undergo 40 Gy of radiation.

Primary outcome measure

Disease Free Survival [ Time Frame: Up to 24 months post initial surgery ]

Central Contacts and Locations

Central contacts

Azeezat Yekinni

317-529-6883 ayekinn@iu.edu

Locations

IU Health Joe and Shelly Schwarz Cancer Center

Recruiting

Carmel, Indiana, United States, 46032

Contacts

Sarah Dutkevitch, RN

317-278-5618 sdutkevi@iu.edu

Principal Investigator:

Michael Sim, MD

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Azeezat Yekinni

317-529-6883 ayekinn@iu.edu

Principal Investigator:

Michael Sim, MD

More Information

Sponsor

Indiana University

Last update posted

Aug 11, 2026

Last verified

Aug, 2026

Keywords

NavDX
HPVctDNA
HPV
transoral surgery

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Indiana University on 2026-08-11.