De-Escalated Adjuvant and Definitive Radiation Therapy Informed by DART 2.0 ctHPV-DNA

May 8, 2026 updated by: Mayo Clinic

DART 2.0: ctHPV-DNA Informed De-Escalated Adjuvant and Definitive Radiation Therapy

This phase II trial examines the use of blood-based biomarkers is to help inform decision making for treatment and radiation therapy for patients with human papillomavirus (HPV) positive oropharyngeal squamous cell cancers. The standard treatments for head and neck cancers are radiation therapy with chemotherapy or surgery potentially followed by radiation therapy with or without chemotherapy. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving chemotherapy along with radiation may kill more tumor cells. However, the cancer can recur or can spread to other parts of the body and all treatments can be associated with side effects. The purpose of this study is to evaluate a blood-based biomarker, using the NavDx testing device, for head and neck cancers in order to see if it can help improve selection of the intensity of treatment in order to best balance the side effects of treatment with the goal of decreasing cancer recurrence. This test could aid in early detection of recurrence and salvage therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To prospectively incorporate circulating tumor human papillomavirus deoxyribonucleic acid (ctHPVDNA) in combination with clinical and pathologic factors to appropriately select patients for treatment intensity.

II. To demonstrate patients traditionally offered adjuvant radiation therapy (RT) but at low risk of treatment failure based on clinical pathologic and post op ctHPVDNA risk factors have an acceptable 1-year progression free survival (PFS) warranting further study. (Favorable Intermediate Risk [GROUP 1]) III. To demonstrate based on clinical, pathologic, and ctHPVDNA risk factors a select population receiving diffusing alpha-emitter radiation therapy (DART) (+ multiple segment radiation therapy [MSRT] where applicable) is associated with acceptable 2 year PFS. (Unfavorable Intermediate Risk [GROUP 2]) IV. To quantify the rate of recurrence as defined by the 2 year PFS in an identified high risk population using the incorporation of ctHPVDNA. (High Risk [GROUP 3]) V. To prospectively use week 4 ctHPVDNA to guide treatment intensity of 56 versus (vs) 70 Gy with concurrent cisplatin to demonstrate 56 Gy with sufficient ctHPVDNA clearance results in an acceptable 2 year PFS. (Chemoradiation Cohort [GROUP 4])

SECONDARY OBJECTIVES:

I. To compare PFS by treatment arm including at landmark timepoints II. To assess the disease-free survival (DFS) in patients that are disease-free post-treatment.

III. To compare overall survival (OS) by treatment arm including at landmark timepoints.

IV. To compare patient reported outcomes (PROS) by treatment arm and modality. V. To evaluate treatment toxicity by Common Terminology Criteria for Adverse Events (CTCAE) criteria as rated by providers across treatment arms.

VI. To define patterns of recurrence by treatment arm. VII. To describe salvage therapy by treatment arm, including the rate, type, and success of salvage treatment.

VIII. To compare functional outcomes by treatment arm based on modified barium swallow study (MBSS) and Functional Oral Intake Scale (FOIS) by treatment arm.

IX. To return to work parameters by treatment arm as assessed by the Work Productivity and Activity Impairment Questionnaire (WPAI).

X. To quantify the costs of return visits for surveillance. XI. To assess end of treatment ctHPVDNA detectability and its association with PFS by comparing patients with detectable versus undetectable end of treatment ctHPVDNA within treatment arms.

XII. To compare outcomes by institution. XIII. To evaluate rates of post operative bleeding, tracheostomy, and readmission with 6 weeks of resection.

XIV. To compare methods of surveillance in diagnosis of recurrence including clinical evaluation, ctHPVDNA testing, and imaging.

XV. To investigate the impact of tobacco and smoking history on recurrence, PFS, and OS.

XVI. To perform a matched analysis of patients by clinical and pathologic risk factors to MC1273, MC1675, and MC Mucosal Sparing (NCT02736786).

CORRELATIVE RESEARCH OBJECTIVES:

I. Will investigate post-op Day 1 or 2 ctHPVDNA detectability as a surrogate for detectability for later post-op timepoints including risk of recurrence rates.

II. Will analyze salivary samples pre-treatment, post-op, and at the time of recurrence to determine whether salivary ctHPVDNA may further inform recurrence risk and surveillance in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC).

III. Will characterize post-operative drain fluid and compare rates of detectability to blood and saliva in order with the aim to determine whether the regional drain represents a separate regional compartment for analysis.

IV. Will prospectively quantify pretreatment imaging for number of involved nodes, radiographic extranodal extension (rENE) as it relates to pathologic findings and risk of recurrence.

V. Will analyze within category of low intermediate, high intermediate, and high-risk patients the percentage of tumor infiltrating lymphocytes (TILs) and association with recurrence as well as differences across treatment groups.

VI. Will assess whether HPV is integrated vs episomal for each patient and the relationship of ctHPVDNA detectability and outcomes.

VII. Will investigate molecular markers on formalin-fixed paraffin-embedded (FFPE) from primary surgical specimens.

OUTLINE: Patients are assigned to 1 of 4 groups.

GROUP I: Patients undergo observation following standard of care surgery. Patients undergo MBSS at pre-operative (pre-op), 2 weeks post-operative (post-op), and 3 months follow-up. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.

GROUP II: Patients undergo DART with/without mucosal sparing twice daily (BID) on days 1-12 Monday-Friday for a total of 20 fractions within 8 weeks of standard of care surgery. Patients receive concurrent docetaxel intravenously (IV) over 1 hour on days 1 and 8 (Mondays preferred). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.

GROUP III: Patients undergo intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) once daily (QD) on days 1-40 Monday-Friday for a total of 30 fractions within 6 weeks of standard of care surgery. Depending on risk status, patients may also receive concurrent cisplatin IV over 1-2 hours once a week (QW) on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.

GROUP IV: Patients undergo IMRT or IMPT therapy QD on days 1-40 Monday-Friday for 28 or 35 fractions based on biomarker response along with concurrent cisplatin IV over 1-2 hours QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS prior to RT and at 3 and 12 months post RT. Patients undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing pre-RT, 4 weeks into RT, anticipated fraction 20, end of RT, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at prior to RT, at the end of RT, at any clinical recurrence.

After completion of study treatment, patients are followed up at 4-6 weeks post treatment, every 3 months post-treatment for 2 years, every 6 months for year 3, and annually for years 4 and 5.

Study Type

Interventional

Enrollment (Estimated)

455

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic in Arizona
        • Principal Investigator:
          • Samir H. Patel, M.D.
        • Contact:
        • Contact:
          • Shelby Watkin
          • Phone Number: 480-342-2000
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Recruiting
        • Mayo Clinic in Florida
        • Contact:
        • Principal Investigator:
          • Adam L. Holtzman, M.D.
        • Contact:
          • Caroline Pamboukas
          • Phone Number: 904-953-2791
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • David M. Routman, M.D.
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • PRE-REGISTRATION (optional): Provide written informed consent
  • Age >= 18 years
  • Histological confirmation of squamous cell carcinoma originating from or suspected to be originating from the oropharynx
  • Plan for gross total surgical resection via trans oral surgery with curative intent and at least unilateral neck dissection OR chemoradiotherapy with cisplatin. Note: The patient must be cisplatin eligible even if an alternate is used due to drug shortage
  • Absence of distant metastases on standard diagnostic work-up =< 16 weeks prior to registration. (Chest CT or PET/CT)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 1
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Provide written informed consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willing to provide blood samples for correlative research purposes, including anonymous shipment of samples to for NavDx testing

Exclusion Criteria:

  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)+
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy =< 5 years prior to registration. EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or prostate or localized endometrioid endometrial cancer. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
  • Prior history of radiation therapy to the affected site
  • Prior systemic chemotherapy in the last 5 years
  • Contraindication to radiation therapy as determined by the treating team
  • History of allergic reaction to docetaxel
  • Receiving any medications or substances which in the opinion of the investigators would interfere with treatment. Examples could include strong inhibitors of cytochrome P450 3A4 (CYP3A4) at oncologist discretion
  • Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the investigator, preclude the use of cisplatin chemotherapy

  • cT4 primary tumor

    • NOTE: Patients with no intermediate risk factors after surgery, low risk patients, as defined by T1, T2, tumors with lymph node less than 3cm, no intermediate or high-risk factors such as lymphatic invasion (LVSI), extranodal extension (ENE), perineural invasion (PNI), positive margin, will be withdrawn from study and be observed per current clinical standard of care. Patients found to be both HPV negative and p16 negative will be withdrawn from study.
    • Patients found to have HPV non 16 type, or HPV detectability in blood less than <20tumor tissue modified viral (TTMV) will not be candidates for de-escalation in Groups 1 and 2 and will be treated in Group 3 unless otherwise meeting criteria for low risk. They will receive 60 Gy +/- cisplatin or acceptable alternate regimen when drug shortages of cisplatin exist. If treated primarily with chemoradiation (chemoRT) (Group 4), these patients will not be candidates for de-escalation if TTMV is < 50 TTMV but can remain on study receiving 70 Gy with all corresponding correlative studies applying
    • Patients with unknown (radiologic/clinically occult) primaries but neck adenopathy suspected to be HPV associated oropharyngeal carcinoma can be registered to go on study for Groups 1-3. Should after primary resection, no primary tumor be identified, the patient will be withdrawn from study and be treated per institutional standard of care. Group 4 patients must have an identifiable (clinically or radiologically apparent) primary tumor
    • All treatment primarily, including surgery and chemotherapy will be performed at the enrolling institution

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group 1 (observation)
Patients undergo observation following standard of care surgery. Patients undergo modified barium swallow study (MBSS) at pre-op, 2 weeks post-op, and 3 months follow-up. Patients also undergo CT, PET/CT, or magnetic MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)
Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Other: Questionnaire
Ancillary studies
Other Names:
  • Questionnaire Administration
Procedure: Modified Barium Swallow Study
Undergo MBSS
Other Names:
  • MBS
  • VFSS
  • Videofluoroscopic Swallowing Study
  • Modified Barium Swallow
Procedure: Biospecimen Collection
Undergo blood and saliva specimen collection for NavDx testing
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Other: Observation Activity
Undergo observation
Other Names:
  • OBSERVATION
Experimental: Group 2 (DART, docetaxel)
Patients undergo DART with/without mucosal sparing BID on days 1-12 Monday-Friday for a total of 20 fractions within 8 weeks of standard of care surgery. Patients receive concurrent docetaxel IV over 1 hour on days 1 and 8 (Mondays preferred). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)
Drug: Docetaxel
Given IV
Other Names:
  • Taxotere
  • Docecad
  • RP56976
  • Taxotere Injection Concentrate
  • RP 56976
  • RP-56976
Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Radiation: Diffusing Alpha-emitter Radiation Therapy
Undergo DART
Other Names:
  • DaRT
Other: Questionnaire
Ancillary studies
Other Names:
  • Questionnaire Administration
Procedure: Modified Barium Swallow Study
Undergo MBSS
Other Names:
  • MBS
  • VFSS
  • Videofluoroscopic Swallowing Study
  • Modified Barium Swallow
Procedure: Biospecimen Collection
Undergo blood and saliva specimen collection for NavDx testing
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Experimental: Group 3 (IMRT/IMPT, with/without cisplatin)
Patients undergo IMRT or IMPT QD on days 1-40 Monday-Friday for a total of 30 fractions within 6 weeks of standard of care surgery. Depending on risk status, patients may also receive concurrent cisplatin IV over 1-2 hours once a week QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Procedure: Intensity-Modulated Proton Therapy
Undergo IMPT
Other Names:
  • IMPT
Other: Questionnaire
Ancillary studies
Other Names:
  • Questionnaire Administration
Procedure: Modified Barium Swallow Study
Undergo MBSS
Other Names:
  • MBS
  • VFSS
  • Videofluoroscopic Swallowing Study
  • Modified Barium Swallow
Procedure: Biospecimen Collection
Undergo blood and saliva specimen collection for NavDx testing
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Experimental: Group 4 (IMRT/IMPT, cisplatin)
Patients undergo IMRT or IMPT therapy QD on days 1-40 Monday-Friday for 28 or 35 fractions based on biomarker response along with concurrent cisplatin IV over 1-2 hours QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS prior to RT and at 3 and 12 months post RT. Patients undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing pre-RT, 4 weeks into RT, anticipated fraction 20, end of RT, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months as well as saliva sample collection at pre-op, end of RT, and any clinical recurrence.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)
Drug: Cisplatin
Given IV
Other Names:
  • CDDP
  • Cis-diamminedichloridoplatinum
  • Cismaplat
  • Cisplatinum
  • Neoplatin
  • Platinol
  • Abiplatin
  • Blastolem
  • Briplatin
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cisplatina
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
Procedure: Intensity-Modulated Proton Therapy
Undergo IMPT
Other Names:
  • IMPT
Procedure: Modified Barium Swallow Study
Undergo MBSS
Other Names:
  • MBS
  • VFSS
  • Videofluoroscopic Swallowing Study
  • Modified Barium Swallow
Procedure: Biospecimen Collection
Undergo blood and saliva specimen collection for NavDx testing
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: From registration to the first of either disease progression/recurrence or death, assessed up to 5 years
Progression-free survival (PFS), the time from treatment initiation until disease progression or worsening. PFS at specific timepoints will be estimated using Kaplan-Meier methodology.
From registration to the first of either disease progression/recurrence or death, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: Up to 5 years
Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Patterns of recurrence and rate of salvage therapy for Low Intermediate Risk (GROUP 1) and multiple segment radiation therapy (MSRT) + de-escalated adjuvant radiation therapy (DART)
Time Frame: Up to 5 years
Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Costs of return visits for surveillance
Time Frame: Up to 5 years
Presented descriptively and ANOVA models with tukey's adjustment for pairwise comparison will be utilized to test difference in arms.
Up to 5 years
Assessment of surveillance circulating human papillomavirus deoxyribonucleic acid (ctHPVDNA) preceding clinical or radiologic detection of recurrence
Time Frame: Up to 5 years
Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Matched analysis of patients by clinical and pathologic risk factor to MC1273 and MC1675 de-escalation arms to overall GROUP 1 and GROUP 2 cohorts including 2-year PFS
Time Frame: Up to 5 years
Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Functional outcomes of DART alone vs. DART + MSRT
Time Frame: Up to 5 years
Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Feasibility of DART regimen outside of Mayo Clinic
Time Frame: Up to 5 years
Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Progression-free survival (PFS) follow-up
Time Frame: At years 1, 2, 3, 4, and 5
Progression-free survival (PFS) is defined as the time from treatment initiation until disease progression or worsening. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response versus (vs.) no response), we'll use logistic regression models.
At years 1, 2, 3, 4, and 5
Disease-free survival (DFS)
Time Frame: From time of surgery and also from end of all treatment across all the groups, assessed up to 5 years
Disease-free survival (DFS) is the measure of time after treatment during which no sign of cancer is found. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
From time of surgery and also from end of all treatment across all the groups, assessed up to 5 years
Overall survival (OS)
Time Frame: At years 1, 2, 3, 4, and 5
Overall survival (OS) is defined as the duration of patient survival from the time of treatment initiation. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
At years 1, 2, 3, 4, and 5
Patient reported outcomes (PROs)
Time Frame: Up to 5 years
Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Functional outcomes - PROs
Time Frame: Up to 5 years
Measure by patient reported outcomes (PROs). Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Proton vs photon treatment toxicity - PROs
Time Frame: Up to 5 years
Assessed by PROs. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Proton vs photon treatment toxicity - MBSS
Time Frame: Up to 5 years
Assessed by MBSS. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Proton vs photon treatment toxicity - dosimetric differences
Time Frame: Up to 5 years
Assessed by dosimetric differences including to organs at risk and the primary tumor bed in the case of mucosal sparing. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Evaluation of end of treatment treatment circulating human papillomavirus deoxyribonucleic acid (ctHPVDNA) detectability as a marker of risk of progression
Time Frame: Up to 5 years
Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Functional outcomes - modified barium swallow study (MBSS)
Time Frame: Up to 5 years
Measured by modified barium swallow (MBSS). Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Evaluation of return to work
Time Frame: Up to 5 years
Will be assessed by the Work Productivity and Activity Impairment Questionnaire (WPAI). Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
ctHPVDNA detectability
Time Frame: At post-operative day 1 or 2
Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
At post-operative day 1 or 2
Characterization of post-operative drain fluid
Time Frame: Up to 5 years
We will characterize post-operative drain fluid and compare rates of detectability to blood and saliva in order with the aim to determine whether the regional drain represents a separate regional compartment for analysis. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Quantification of pre-treatment imaging
Time Frame: Up to 5 years
We will prospectively quantify pretreatment imaging for number of involved nodes, radiographic extranodal extension as it relates to pathologic findings and risk of recurrence. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Percentage of tumor infiltrating lymphocytes (TILs)
Time Frame: Up to 5 years
We will analyze within category of low intermediate, high intermediate, and high-risk patients the percentage of TILs and association with recurrence as well as differences across treatment groups. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Assessment of integrated vs episomal HPV
Time Frame: Up to 5 years
Comparison of methods of surveillance as defined by the date of diagnosis of recurrence by ctHPVDNA testing as compared to clinical examination and imaging. Sensitivity, specificity, negative predictive value, and positive predictive value of each will be reported. Measure whether HPV is integrated vs episomal for each patient and the relationship of ctHPVDNA detectability and outcomes. These analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Assess Molecular Markers Using FFPE
Time Frame: Up to 5 years
We will investigate molecular markers on formalin-fixed paraffin-embedded (FFPE) from primary surgical specimens. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years
Salivary ctHPVDNA analysis for recurrence risk and surveillance
Time Frame: Up to 5 years
Salivary samples will be analyzed pre-treatment, post-op, and at the time of recurrence to determine whether salivary ctHPVDNA may further inform recurrence risk and surveillance in HPV(+) oropharyngeal squamous cell carcinoma. Due to the limited sample size, these analyses will be hypothesis generating and descriptive in nature. Descriptive statistics will be summarized and the exploratory data will be correlated with clinical endpoints (PFS, time-to-progression, etc.). For time-to-event data, the Kaplan-Meier method will be used. For categorical data, we'll use the Fisher's exact test. For biomarker data used to predict binary outcomes (i.e. response vs. no response), we'll use logistic regression models.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Investigators

  • Principal Investigator: David M, Routman, M.D., Mayo Clinic in Rochester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2023

Primary Completion (Estimated)

August 1, 2028

Study Completion (Estimated)

August 1, 2029

Study Registration Dates

First Submitted

August 30, 2022

First Submitted That Met QC Criteria

September 12, 2022

First Posted (Actual)

September 15, 2022

Study Record Updates

Last Update Posted (Actual)

May 12, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GMROR2271
  • 22-004443 (Other Identifier: Mayo Clinic in Rochester)
  • DART 2.0 (Other Identifier: Mayo Clinic in Rochester)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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