Phase II Clinical Trial of De-Intensified Therapy in Human Papilloma Virus (HPV) Associated Oropharyngeal Squamous Cell Carcinoma

Phase 2

Not yet recruiting

• Conditions: OPSCC; Oropharyngeal Squamous Cell Carcinoma (SCC); HPV Associated Cancers

• Registration Number: NCT06759155
• Lead Sponsor: University of Vermont Medical Center

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-12-19
• Study First Submitted QC: 2024-12-27
• Last Update Submitted: 2024-12-27
• Study Start: 2025-01
• Study First Posted: 2025-01-06
• Last Update Posted: 2025-01-06
• Primary Completion: 2030-01
• Study Completion: 2030-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring overall survival.	from enrollment to 5 year follow-up	Overall survival will be monitored.
Safety and tolerability	from enrollment to 5 year follow-up	The study will use the CTCAE version 5.0 for reporting of non-hematologic adverse events.
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring progression free survival.	from enrollment to 5 year follow-up	Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring progression free survival.
Assess oncologic outcomes of a de-intensified post-surgical adjuvant treatment by measuring locoregional control.	from enrollment to 5 year follow-up	Locoregional control (LRC) is defined as time from treatment initiation to local or regional recurrence

Secondary Outcome Measures

Name	Time	Method
Evaluate how changes in serum HPV ctDNA are associated\ with HPV-positive OPSCC recurrence	from enrollment to 5 year follow-up	ctDNA will be measured at baseline and at several points during follow-up. The sensitivity, specificity and concordance of the HPV ctDNA results in relation to the clinical and pathologic disease status (presence/absence) will be corelated.