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Selective Adjuvant Therapy for HPV-mediated Oropharynx SCCs Based on Residual Circulating Tumor DNA Levels (SAVAL) (SAVAL)

Primary Purpose

Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Oropharynx Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Experimental Observation
Observation per Standard of Care
Adjuvant Treatment per Standard of Care
Circulating Tumor DNA test (ctDNA test)
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring Transoral Robotic Surgery (TORS), Head and Neck Cancer, Oropharynx Cancer, HPV p16 Oropharynx Cancer, Proton Therapy, Photon Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria 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. 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? Has the patient completed a ctDNA evaluation with results demonstrating positive ctDNA levels prior to surgery either in blood or on biopsy tissue? Upon multi-disciplinary review, is the patient a candidate for TORS based on evaluation by ENT and review at multi-disciplinary tumor board? 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? Was the patient's Zubrod Performance Status 0-1 within 30 days prior to registration? Is the patient ≥ 18 years of age? 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. 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 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? Does the patient have distant metastasis? 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? Did the patient have prior systemic chemotherapy for the study cancer (prior chemotherapy for a different cancer is allowable)? Did the patient have prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields? Did the patient have prior cancer related surgeries of the head and neck excluding superficial removal of cutaneous skin malignancies? Does the patient have any co-morbid condition or concern that may interfere with follow up per experimental arm? Does the patient have an active drug or alcohol dependency that in the opinion of the investigator would limit compliance with study requirements? Is the patient pregnant or nursing (an exception will be made for nursing patients that are not receiving chemotherapy)?

Sites / Locations

  • Maryland Proton Treatment Center
  • UMMC
  • University of Maryland Greenebaum Cancer Center
  • Upper Chesapeake Health
  • Central Maryland Radiation Oncology
  • Baltimore Washington Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intermediate Risk Experimental Observation

Arm Description

Requires the following criteria: pT1-3pN1-2 with negative surgical margins Absent or microscopic ECE (≤1mm) 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).

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS)
Percent PFS at 2 year post last treatment inclusive of patients undergoing salvage treatment for LRR.

Secondary Outcome Measures

Rate of Recurrence
Rate of recurrence at one year post TORS with negative ctDNA
Rate of Salvage
Rate of salvage for locoregional recurrence (LRR) after TORS
Locoregional recurrence (LRR)
Overall Survival (OS)
Number of participants free from distant metastases
Freedom from Distant Metastases (FFDM) at 2 years post last treatment
Grade 2/3 xerostomia
defined by PRO-CTCAE (patient-reported outcome (PRO) measurement system - Common Terminology Criteria for Adverse Events (CTCAE))
Patient scores from the questionnaire called The M.D. Anderson Dysphagia Inventory (MDADI)
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.
PEG-tube rate
Percutaneous endoscopic gastrostomy (PEG)-tube rate

Full Information

First Posted
September 28, 2023
Last Updated
October 16, 2023
Sponsor
University of Maryland, Baltimore
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1. Study Identification

Unique Protocol Identification Number
NCT06088381
Brief Title
Selective Adjuvant Therapy for HPV-mediated Oropharynx SCCs Based on Residual Circulating Tumor DNA Levels (SAVAL)
Acronym
SAVAL
Official Title
A Single Arm Phase II Trial Evaluating Selective Adjuvant Therapy for HPV-mediated Oropharynx SCCs Based on Residual Circulating Tumor DNA Levels (SAVAL)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 18, 2023 (Anticipated)
Primary Completion Date
October 18, 2025 (Anticipated)
Study Completion Date
October 18, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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 surgery (TORS) or RT(+/- 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 +/- chemo) per SOC.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, Oropharynx Cancer, Oropharynx Squamous Cell Carcinoma, HPV Positive Oropharyngeal Squamous Cell Carcinoma
Keywords
Transoral Robotic Surgery (TORS), Head and Neck Cancer, Oropharynx Cancer, HPV p16 Oropharynx Cancer, Proton Therapy, Photon Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
61 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intermediate Risk Experimental Observation
Arm Type
Experimental
Arm Description
Requires the following criteria: pT1-3pN1-2 with negative surgical margins Absent or microscopic ECE (≤1mm) 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).
Intervention Type
Other
Intervention Name(s)
Experimental Observation
Intervention Description
Patients on the experimental arm will be under observation only.
Intervention Type
Other
Intervention Name(s)
Observation per Standard of Care
Intervention Description
The low-risk group of patients will be observed per standard of care.
Intervention Type
Radiation
Intervention Name(s)
Adjuvant Treatment per Standard of Care
Intervention Description
The high-risk group of patients will receive adjuvant treatment per standard of care (Radiation with or without chemotherapy)
Intervention Type
Diagnostic Test
Intervention Name(s)
Circulating Tumor DNA test (ctDNA test)
Intervention 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.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
Percent PFS at 2 year post last treatment inclusive of patients undergoing salvage treatment for LRR.
Time Frame
2 year post last treatment
Secondary Outcome Measure Information:
Title
Rate of Recurrence
Description
Rate of recurrence at one year post TORS with negative ctDNA
Time Frame
1 year post TORS
Title
Rate of Salvage
Description
Rate of salvage for locoregional recurrence (LRR) after TORS
Time Frame
2 years post TORS
Title
Locoregional recurrence (LRR)
Time Frame
2 year post last treatment
Title
Overall Survival (OS)
Time Frame
2 year post last treatment
Title
Number of participants free from distant metastases
Description
Freedom from Distant Metastases (FFDM) at 2 years post last treatment
Time Frame
2 year post last treatment
Title
Grade 2/3 xerostomia
Description
defined by PRO-CTCAE (patient-reported outcome (PRO) measurement system - Common Terminology Criteria for Adverse Events (CTCAE))
Time Frame
1-year following completion of treatment
Title
Patient scores from the questionnaire called The M.D. Anderson Dysphagia Inventory (MDADI)
Description
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.
Time Frame
1-year following completion of treatment
Title
PEG-tube rate
Description
Percutaneous endoscopic gastrostomy (PEG)-tube rate
Time Frame
2-year following completion of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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. 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? Has the patient completed a ctDNA evaluation with results demonstrating positive ctDNA levels prior to surgery either in blood or on biopsy tissue? Upon multi-disciplinary review, is the patient a candidate for TORS based on evaluation by ENT and review at multi-disciplinary tumor board? 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? Was the patient's Zubrod Performance Status 0-1 within 30 days prior to registration? Is the patient ≥ 18 years of age? 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. 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 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? Does the patient have distant metastasis? 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? Did the patient have prior systemic chemotherapy for the study cancer (prior chemotherapy for a different cancer is allowable)? Did the patient have prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields? Did the patient have prior cancer related surgeries of the head and neck excluding superficial removal of cutaneous skin malignancies? Does the patient have any co-morbid condition or concern that may interfere with follow up per experimental arm? Does the patient have an active drug or alcohol dependency that in the opinion of the investigator would limit compliance with study requirements? Is the patient pregnant or nursing (an exception will be made for nursing patients that are not receiving chemotherapy)?
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jason K Molitoris, MD, PhD
Phone
410-328-6080
Email
jmolitoris@umm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kelly Kitzmiller, MPH
Phone
410-369-5264
Email
kelly.kitzmiller@umm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jason K Molitoris, MD, PhD
Organizational Affiliation
University of Maryland/Maryland Proton Treatment Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maryland Proton Treatment Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
UMMC
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Maryland Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Upper Chesapeake Health
City
Bel Air
State/Province
Maryland
ZIP/Postal Code
21014
Country
United States
Facility Name
Central Maryland Radiation Oncology
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21044
Country
United States
Facility Name
Baltimore Washington Medical Center
City
Glen Burnie
State/Province
Maryland
ZIP/Postal Code
21061
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Selective Adjuvant Therapy for HPV-mediated Oropharynx SCCs Based on Residual Circulating Tumor DNA Levels (SAVAL)

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