ctHPVDNA in HPV Positive Squamous Cell Carcinoma of the Oropharynx

Official title

Circulating Tumor HPV DNA Driven Adjuvant Treatment Deintensification After Transoral Surgery for HPV-Positive Squamous Cell Carcinoma of the Oropharynx

Overview

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.

Detailed 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.

Interventions

• Diagnostic test 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.
• Radiation 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.
• Radiation 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 measures

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

Secondary outcome measures (6)

• Local-reginal Control [Time frame: Up to 24 months post initial surgery]
• Overall Survival [Time frame: Up to 24 months post initial surgery]
• Distant metastasis rates [Time frame: Up to 24 months post initial surgery]
• Adverse Events [Time frame: up to 6 months post initial surgery]
• Swallowing-related Quality Of Life [Time frame: 3 months, 6 months, 12 months, and 24 months post initial surgery]
• Gastrostomy tube dependence rates [Time frame: 12 and 24 months post intial surgery]

Eligibility criteria

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:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• IU Health Joe and Shelly Schwarz Cancer Center — Carmel
• Indiana University Melvin and Bren Simon Comprehensive Cancer Center — Indianapolis

Identifiers

NCT: NCT06915038 · CTO-IUSCCC-0895

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗