Selective Adjuvant Therapy for HPV-mediated Oropharynx SCCs Based on Residual Circulating Tumor DNA Levels (SAVAL)
- Conditions
- Head and Neck CancerHead and Neck Squamous Cell CarcinomaOropharynx CancerOropharynx Squamous Cell CarcinomaHPV Positive Oropharyngeal Squamous Cell Carcinoma
- Interventions
- Other: Experimental ObservationOther: Observation per Standard of CareRadiation: Adjuvant Treatment per Standard of CareDiagnostic Test: Circulating Tumor DNA test (ctDNA test)
- Registration Number
- NCT06088381
- Lead Sponsor
- University of Maryland, Baltimore
- Brief Summary
Patients with human papillomavirus (HPV)-related oropharyngeal cancer generally have favorable outcomes and how well they do depends on the specific details about the patient and their cancer. How well they do isn't as related to the kinds of treatment they get. However, there are significant side effects for the various types of treatments they may get. Because these patients generally have favorable outcomes no matter the kind of treatment, reducing side effects should be a priority when choosing their treatment.
The goal of this clinical research study is to evaluate whether a new blood test called a Circulating Tumor DNA test (ctDNA test) can decrease the number of people that require radiation after surgery. This blood test is often elevated in people when they are diagnosed with head and neck cancer. There are studies that show that cancer most often returns when this blood test is positive after treatment. This study will test patients' blood before and after surgery. In cases where the test is negative after surgery, people on the study will not receive radiation unless they are considered high risk based on surgery findings. The hope is that radiation and its potential side effects can be limited to only people that need the treatment.
- Detailed Description
Patients with human papillomavirus (HPV) or its surrogate marker p16, positive oropharyngeal squamous cell carcinoma (hereafter p16+OPSCC) exhibit favorable overall survival rates of 70-100% at 3 years. These outcomes are dependent on disease burden and patient characteristics and independent of treatment modality. Significant treatment related side effects exist despite advances in radiotherapy technology, surgical techniques, and supportive care. In addition to common acute toxicities, their favorable overall survival potentially places these patients at increased risk for developing long-term treatment-induced side-effects. Therefore, it is important to establish novel management approaches that maintain excellent current clinical outcomes while effectively reducing acute and long-term side effects.
The de-escalation trials for surgical management have explored various combinations of dose-reduction, while preserving favorable oncologic outcomes for patients. Prospective trials have demonstrated efficacy, safety, and functional benefit following treatment reduction to the primary tumor, regional lymph node metastasis, and the elective nodal volume. Therefore, newer approaches of combining the treatment modifications from each of these treatment fields offer the potential to have substantial harm reduction for future patients.
Cell free HPV tumor DNA (ctDNA) has emerged as a method to monitor the presence of disease and is a promising biomarker. Changes in expression of ctDNA post treatment with TransOral Robotic Surgery (TORS) or radiation therapy (RT) with or without chemotherapy are observed and clearance of ctDNA is associated with a favorable prognosis. These promising findings have led several groups to initiate clinical trials evaluating observation in patients after definitive oropharyngeal cancer removal and subsequent clearance of ctDNA levels. Data suggests that patients who initially undergo observation following TORS have similar rates of distant metastases and favorable rates of salvage. To date, an observation-based approach has not been adopted for intermediate risk patients due to challenges identifying optimal cohorts for observation and concern for increased treatment related toxicity for patients who do require salvage. In this trial, the investigators propose use of ctDNA clearance to identify patients who are optimal for observation. This protocol tests the hypothesis that patients currently recommended for adjuvant RT based on intermediate risk factors can be observed post-TORS when ctDNA is cleared.
Patients with p16+OPSCC who are candidates for surgery (TORS) and have positive ctDNA will be offered registration for the study prior to surgical resection. After TORS, all patients will have ctDNA drawn within 2-14 days post operatively. Combined with pathological criteria, all patients will be stratified into one three risk groups; low risk, intermediate risk, high risk. The low risk group will be observed (no radiation) per standard of care (SOC). The intermediate group (intermediate pathological features and negative ctDNA) will also be observed (no radiation) per the experimental arm. The high risk group will receive adjuvant treatment (RT +/- chemotherapy) per SOC.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 61
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Intermediate Risk Experimental Observation Experimental Observation Requires the following criteria: 1. Pathological T1-3 N1-2 with negative surgical margins 2. Absent or microscopic extracapsular extension(ECE) (≤1mm) 3. ctDNA positive pre-operatively and negative post-operatively This group will undergo observation on the experimental arm of the study. They will be monitored for toxicity, Quality of Life (QoL) and outcomes evaluation. Suspected locoregional recurrence (LRR) based on physical examination, imaging or increasing ctDNA will undergo completion of workup at the discretion of the University of Maryland Head and Neck tumor board. LRR will be offered salvage treatment based on recommendations from multi-disciplinary discussion. Salvage therapy could include surgical resection (with or without adjuvant treatment), and definitive RT (with or without chemotherapy). Intermediate Risk Experimental Observation Observation per Standard of Care Requires the following criteria: 1. Pathological T1-3 N1-2 with negative surgical margins 2. Absent or microscopic extracapsular extension(ECE) (≤1mm) 3. ctDNA positive pre-operatively and negative post-operatively This group will undergo observation on the experimental arm of the study. They will be monitored for toxicity, Quality of Life (QoL) and outcomes evaluation. Suspected locoregional recurrence (LRR) based on physical examination, imaging or increasing ctDNA will undergo completion of workup at the discretion of the University of Maryland Head and Neck tumor board. LRR will be offered salvage treatment based on recommendations from multi-disciplinary discussion. Salvage therapy could include surgical resection (with or without adjuvant treatment), and definitive RT (with or without chemotherapy). Intermediate Risk Experimental Observation Circulating Tumor DNA test (ctDNA test) Requires the following criteria: 1. Pathological T1-3 N1-2 with negative surgical margins 2. Absent or microscopic extracapsular extension(ECE) (≤1mm) 3. ctDNA positive pre-operatively and negative post-operatively This group will undergo observation on the experimental arm of the study. They will be monitored for toxicity, Quality of Life (QoL) and outcomes evaluation. Suspected locoregional recurrence (LRR) based on physical examination, imaging or increasing ctDNA will undergo completion of workup at the discretion of the University of Maryland Head and Neck tumor board. LRR will be offered salvage treatment based on recommendations from multi-disciplinary discussion. Salvage therapy could include surgical resection (with or without adjuvant treatment), and definitive RT (with or without chemotherapy). Intermediate Risk Experimental Observation Adjuvant Treatment per Standard of Care Requires the following criteria: 1. Pathological T1-3 N1-2 with negative surgical margins 2. Absent or microscopic extracapsular extension(ECE) (≤1mm) 3. ctDNA positive pre-operatively and negative post-operatively This group will undergo observation on the experimental arm of the study. They will be monitored for toxicity, Quality of Life (QoL) and outcomes evaluation. Suspected locoregional recurrence (LRR) based on physical examination, imaging or increasing ctDNA will undergo completion of workup at the discretion of the University of Maryland Head and Neck tumor board. LRR will be offered salvage treatment based on recommendations from multi-disciplinary discussion. Salvage therapy could include surgical resection (with or without adjuvant treatment), and definitive RT (with or without chemotherapy).
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) 2 year post last treatment Percent PFS at 2 year post last treatment inclusive of patients undergoing salvage treatment for LRR.
- Secondary Outcome Measures
Name Time Method Rate of Salvage 2 years post TORS Rate of salvage for locoregional recurrence (LRR) after TORS
Patient scores from the questionnaire called The Monroe Dunaway Anderson Dysphagia Inventory (MDADI) 1-year following completion of treatment The M.D. Anderson Dysphagia Inventory is a self-administered questionnaire designed specifically for evaluating the impact of dysphagia on the Quality of Life (QOL) of patients with head and neck cancer.
Two scores are obtained: a Global Score and a Composite Score. Global Score ranges from 1 (extremely low functioning) to 5 (high functioning) Composite Score ranges from 20 (extremely low functioning) to 100 (high functioning)Rate of recurrence in all patients (Groups 1, 2 and 3) stratified by group and post TORS ctDNA levels 1 year post TORS Rate of recurrence stratified by group and post TORS ctDNA levels
Rate of Recurrence 1 year post TORS Rate of recurrence at one year post TORS with negative ctDNA
Number of participants free from distant metastases 2 year post last treatment Freedom from Distant Metastases (FFDM) at 2 years post last treatment
Overall Survival (OS) 2 year post last treatment PEG-tube rate 2-year following completion of treatment Percutaneous endoscopic gastrostomy (PEG)-tube rate
Locoregional recurrence (LRR) 2 year post last treatment Number of participants with grade 2/3 xerostomia 1-year following completion of treatment defined by PRO-CTCAE (patient-reported outcome (PRO) measurement system - Common Terminology Criteria for Adverse Events (CTCAE))
Trial Locations
- Locations (5)
Maryland Proton Treatment Center
🇺🇸Baltimore, Maryland, United States
Baltimore Washington Medical Center
🇺🇸Glen Burnie, Maryland, United States
Central Maryland Radiation Oncology
🇺🇸Columbia, Maryland, United States
University of Maryland Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Upper Chesapeake Health
🇺🇸Bel Air, Maryland, United States