Clinical trial NCT06759155: Phase II Clinical Trial of De-Intensified Therapy in Human Papilloma Virus (HPV) Associated Oropharyngeal Squamous Cell Carcinoma
Official title: Phase II Clinical Trial of De-Intensified Therapy in Human Papilloma Virus (HPV) Associated Oropharyngeal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: OPSCC
Oropharyngeal Squamous Cell Carcinoma (SCC)
HPV Associated Cancers
Keywords: radiation
de-intensify
Lead sponsor: University of Vermont Medical Center
Sponsor class: OTHER
First posted: 2025-01-06
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be stratified into 4 groups depending on their risk factors. Groups A and be will not receive radiation (de-intensified), group C will receive a de-intensified level of radiation, group D will receive standard of care radiation (not de-intensified).
Primary purpose: TREATMENT

Brief summary: HPV-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) is a type of cancer that affects parts of the throat, like the tonsils and the base of the tongue. The treatments for OPSCC, which may include surgery, radiation, and chemotherapy, often cause serious side effects, such as loss of taste, dry mouth, and long-term problems with swallowing. These side effects can lower patients' quality of life and make it difficult for them to eat and speak normally.

This study aims to explore whether using lower doses of radiation after surgery can help improve long-term swallowing function in patients with HPV-positive OPSCC. By doing this, the study team hopes to reduce treatment-related side effects while maintaining good cancer control.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed or suspected HPV associated squamous cell carcinoma of the oropharynx.
* p16 immunohistochemistry is the surrogate marker for HPV positivity and will be scored as positive if there is strong and diffuse nuclear and cytoplasmic staining present in greater than 70% of the tumor specimen. (A negative result excludes the patient from the trial)
* In the case of equivocal p16, High Risk HPV (HR HPV), In-Situ Hybridization (ISH) / Polymerase Chain Reaction (PCR) may be performed to determine HPV positivity
* AJCC TNM 7th edition stage T1-T3, N0-N2b (or AJCC TNM 8th edition stage T1-T3 N0-N1) disease.
* Staging will be based on cross sectional imaging investigations and clinical exam.
* Patients who initially have an unknown primary but subsequently have a primary site identified on pathology after surgical resection may be included in the study.
* Multidisciplinary team decision to treat with primary transoral resection and neck dissection.
* Patients considered fit for surgery and adjuvant therapy.
* Aged 18 or over.
* Written informed consent provided.

Exclusion Criteria:

* HPV negative squamous cell carcinomas of the head and neck
* T4 and/or T1-T3 tumors where transoral surgery is considered not feasible or there is a high likelihood of positive margins.
* AJCC TNM 7th edition N2c-N3 nodal disease (or AJCC TNM 8th edition N2-N3 nodal disease) or high likelihood of gross extranodal extension.
* Patients for whom transoral surgery and neck dissection is not considered the primary treatment modality.
* Distant metastatic disease as determined by routine pre-operative staging radiological investigations e.g. CT thorax and upper abdomen or PET CT.
* Women who are pregnant or breastfeeding
* Prior history of radiation to head and neck

Primary outcomes:
measure: Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring overall survival.
timeFrame: from enrollment to 5 year follow-up
measure: Safety and tolerability
timeFrame: from enrollment to 5 year follow-up
measure: Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring progression free survival.
timeFrame: from enrollment to 5 year follow-up
measure: Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring locoregional control.
timeFrame: from enrollment to 5 year follow-up
Secondary outcomes:
measure: Evaluate how changes in serum HPV ctDNA are associated\ with HPV-positive OPSCC recurrence
timeFrame: from enrollment to 5 year follow-up
Other outcomes:
Locations:
Study officials:
References: