Trial Title:
Selective Adjuvant Therapy for HPV-mediated Oropharynx SCCs Based on Residual Circulating Tumor DNA Levels (SAVAL)
NCT ID:
NCT06088381
Condition:
Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Oropharynx Cancer
Oropharynx Squamous Cell Carcinoma
HPV Positive Oropharyngeal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Squamous Cell Carcinoma of Head and Neck
Oropharyngeal Neoplasms
Conditions: Keywords:
Transoral Robotic Surgery (TORS)
Head and Neck Cancer
Oropharynx Cancer
HPV p16 Oropharynx Cancer
Proton Therapy
Photon Therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Experimental Observation
Description:
Patients on the experimental arm will be under observation only.
Arm group label:
Intermediate Risk Experimental Observation
Intervention type:
Other
Intervention name:
Observation per Standard of Care
Description:
The low-risk group of patients will be observed per standard of care.
Arm group label:
Intermediate Risk Experimental Observation
Intervention type:
Radiation
Intervention name:
Adjuvant Treatment per Standard of Care
Description:
The high-risk group of patients will receive adjuvant treatment per standard of care
(Radiation with or without chemotherapy)
Arm group label:
Intermediate Risk Experimental Observation
Intervention type:
Diagnostic Test
Intervention name:
Circulating Tumor DNA test (ctDNA test)
Description:
Blood test for diagnostic and surveillance purposes measuring expression of Cell free HPV
tumor DNA (ctDNA) in the blood. Patients will undergo ctDNA within 90 days pre-transoral
robotic surgery(TORS), 2-14 days post TORS, then every 3 months (except for at 21 months)
for 2 year post completion of initial therapy or salvage therapy.
Arm group label:
Intermediate Risk Experimental Observation
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria
1. Is there pathologically (histologically or cytologically) proven diagnosis of p16+
squamous cell carcinoma (including the histological variants papillary squamous cell
carcinoma and basaloid squamous cell carcinoma) of the oropharynx or p16+ squamous
cell carcinoma unknown primary? Note: specimen from cervical lymph nodes with a
well-defined primary site documented clinically or radiologically is acceptable; in
patients with carcinoma of unknown primary this will be sufficient for pathologic
confirmation without a clinically or radiographically defined primary site.
2. Does the patient have clinical stage T0-3, N0-N1, and M0 disease (AJCC 8th edition)
as defined by physical examination and appropriate imaging (PET/CT preferred, CT
neck with IV contrast with CT chest without contrast as recommended alternative to
PET/CT) with imaging within 60 days of enrollment?
3. Has the patient completed a ctDNA evaluation with results demonstrating positive
ctDNA levels prior to surgery either in blood or on biopsy tissue?
4. Upon multi-disciplinary review, is the patient a candidate for TORS based on
evaluation by ear, nose, throat (ENT) and review at multi-disciplinary tumor board?
5. Was a general history and physical examination performed by a radiation oncologist,
medical oncologist, or head and neck surgeon within 60 days prior to registration?
6. Was the patient's Zubrod Performance Status 0-1 within 30 days prior to
registration?
7. Is the patient ≥ 18 years of age?
8. If a woman of child-bearing potential or sexually active male, is the patient
willing to use effective contraception throughout their participation in the
treatment phase of the study and at least 180 days following the last study
treatment.
9. Did the patient provide study specific informed consent prior to study entry,
including consent for mandatory submission of tissue for required p16 review?
Exclusion Criteria
1. Does the patient have cancer considered to be from an oral cavity site (oral tongue,
floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx?
2. Does the patient have distant metastasis?
3. Does the patient have prior invasive malignancy (except non-melanomatous skin cancer
and low/intermediate risk prostate cancer) unless disease free for a minimum of 3
years?
4. Did the patient have prior systemic chemotherapy for the study cancer (prior
chemotherapy for a different cancer is allowable)?
5. Did the patient have prior radiotherapy to the region of the study cancer that would
result in overlap of radiation therapy fields?
6. Did the patient have prior cancer related surgeries of the head and neck excluding
superficial removal of cutaneous skin malignancies?
7. Does the patient have any co-morbid condition or concern that may interfere with
follow up per experimental arm?
8. Does the patient have an active drug or alcohol dependency that in the opinion of
the investigator would limit compliance with study requirements?
9. Is the patient pregnant or nursing (an exception will be made for nursing patients
that are not receiving chemotherapy)?
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Maryland Proton Treatment Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kelly Kitzmiller
Phone:
410-369-5246
Email:
kelly.kitzmiller@umm.edu
Facility:
Name:
University of Maryland Greenebaum Cancer Center
Address:
City:
Baltimore
Zip:
21201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kelly Kitzmiller, BS
Phone:
410-369-5246
Email:
kelly.kitzmiller@umm.edu
Facility:
Name:
Upper Chesapeake Health
Address:
City:
Bel Air
Zip:
21014
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Lalicia Roman
Phone:
443-643-1877
Email:
lalicia.roman@umm.edu
Facility:
Name:
Central Maryland Radiation Oncology
Address:
City:
Columbia
Zip:
21044
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Kelly Kitzmiller
Phone:
410-369-5246
Email:
kelly.kitzmiller@umm.edu
Facility:
Name:
Baltimore Washington Medical Center
Address:
City:
Glen Burnie
Zip:
21061
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Pilar Strycula
Email:
P.Strycula@umm.edu
Contact backup:
Last name:
Pilar
Start date:
March 7, 2024
Completion date:
October 18, 2027
Lead sponsor:
Agency:
University of Maryland, Baltimore
Agency class:
Other
Source:
University of Maryland, Baltimore
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06088381
