ctHPVDNA in HPV Positive Squamous Cell Carcinoma of the Oropharynx

Indiana University

Status: Enrolling

Conditions: Squamous Cell Carcinoma of Oropharynx; Tonsil Cancer; HPV Positive Cancer; Throat Cancer

Treatments: Diagnostic Test: NavDx; Radiation: Adjuvant Radiation 30 Gray; Radiation: Adjuvant Radiation 40 Gray

Study type: Interventional

Funder types: Other

Identifiers

NCT06915038

CTO-IUSCCC-0895

Details and patient eligibility

About

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.

Full description

Oropharyngeal squamous cell carcinoma (OPSCC), commonly known as throat cancer or tonsil cancer, has seen a dramatic rise in incidence over the last twenty years due to the increased incidence of human papillomavirus-positive (HPV) infection and * malignancy within the oropharynx.

The prevailing treatment philosophy within head and neck oncology is that deintensifying treatment could still provide equivalent oncologic outcomes, while further lowering toxicity profiles and improving functional outcomes to minimize the morbidity incurred by patients.

The next frontier in the treatment of HPV+ OPSCC, then, is the potential use of ctHPVDNA in the treatment personalization. Patients could be stratified into risk categories based on their ctHPVDNA levels, and in turn, receive a tailored treatment intensity accordingly.

The goal of this research study is to see if de-intensifying (stopping or scaling back) treatment still provides the same, or perhaps even better, results when compared to standard treatment when using your ctHPVDNA test results as a guide for your treatment.

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.
• Mobile neck nodes on physical exam if N positive.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

Observation

Experimental group

Description:

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

Treatment:

Diagnostic Test: NavDx

Adjuvant Radiation 30 Gray

Experimental group

Description:

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.

Treatment:

Radiation: Adjuvant Radiation 30 Gray

Diagnostic Test: NavDx

Adjuvant Radiation 40 Gray

Experimental group

Description:

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.

Treatment:

Radiation: Adjuvant Radiation 40 Gray

Diagnostic Test: NavDx