The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Blood-Based Biomarkers to Inform Treatment and Radiation Therapy Decisions for HPV Associated Oropharyngeal Squamous Cell Head and Neck Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05541016
Recruitment Status : Recruiting
First Posted : September 15, 2022
Last Update Posted : January 17, 2024
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Oropharyngeal Human Papillomavirus-Positive Squamous Cell Carcinoma Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Procedure: Biospecimen Collection Drug: Cisplatin Procedure: Computed Tomography Radiation: Diffusing Alpha-emitter Radiation Therapy Drug: Docetaxel Procedure: Intensity-Modulated Proton Therapy Radiation: Intensity-Modulated Radiation Therapy Procedure: Magnetic Resonance Imaging Procedure: Modified Barium Swallow Study Other: Observation Procedure: Positron Emission Tomography Other: Quality-of-Life Assessment Other: Questionnaire Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: DART 2.0: ctHPV-DNA Informed De-Escalated Adjuvant and Definitive Radiation Therapy
Actual Study Start Date : February 21, 2023
Estimated Primary Completion Date : August 1, 2028
Estimated Study Completion Date : August 1, 2029

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.
Procedure: Biospecimen Collection
Undergo blood specimen collection for NavDx testing
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)

Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)

Procedure: Modified Barium Swallow Study
Undergo MBSS
Other Names:
  • MBS
  • Modified Barium Swallow
  • VFSS
  • Videofluoroscopic Swallowing Study

Other: Observation
Undergo observation
Other Names:
  • Inspection
  • Visual Inspection

Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • Positron emission tomography (procedure)

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire
Ancillary studies
Other Name: Questionnaire Administration

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.
Procedure: Biospecimen Collection
Undergo blood specimen collection for NavDx testing
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)

Radiation: Diffusing Alpha-emitter Radiation Therapy
Undergo DART
Other Name: DaRT

Drug: Docetaxel
Given IV
Other Names:
  • Docecad
  • RP56976
  • Taxotere
  • Taxotere Injection Concentrate
  • RP 56976

Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)

Procedure: Modified Barium Swallow Study
Undergo MBSS
Other Names:
  • MBS
  • Modified Barium Swallow
  • VFSS
  • Videofluoroscopic Swallowing Study

Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • Positron emission tomography (procedure)

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire
Ancillary studies
Other Name: Questionnaire Administration

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.
Procedure: Biospecimen Collection
Undergo blood specimen collection for NavDx testing
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)

Procedure: Intensity-Modulated Proton Therapy
Undergo IMPT
Other Name: IMPT

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: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)

Procedure: Modified Barium Swallow Study
Undergo MBSS
Other Names:
  • MBS
  • Modified Barium Swallow
  • VFSS
  • Videofluoroscopic Swallowing Study

Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • Positron emission tomography (procedure)

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire
Ancillary studies
Other Name: Questionnaire Administration

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.
Procedure: Biospecimen Collection
Undergo blood specimen collection for NavDx testing
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

Drug: Cisplatin
Given IV
Other Names:
  • Abiplatin
  • Blastolem
  • Briplatin
  • CDDP
  • Cis-diammine-dichloroplatinum
  • Cis-diamminedichloridoplatinum
  • Cis-diamminedichloro Platinum (II)
  • Cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cis-platinous Diamine Dichloride
  • Cis-platinum
  • Cis-platinum II
  • Cis-platinum II Diamine Dichloride
  • Cismaplat
  • Cisplatina
  • Cisplatinum
  • Cisplatyl
  • Citoplatino
  • Citosin
  • Cysplatyna
  • DDP
  • Lederplatin
  • Metaplatin
  • Neoplatin
  • Peyrone's Chloride
  • Peyrone's Salt
  • Placis
  • Plastistil
  • Platamine
  • Platiblastin
  • Platiblastin-S
  • Platinex
  • Platinol
  • Platinol- AQ
  • Platinol-AQ
  • Platinol-AQ VHA Plus
  • Platinoxan
  • Platinum
  • Platinum Diamminodichloride
  • Platiran
  • Platistin
  • Platosin

Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)

Procedure: Intensity-Modulated Proton Therapy
Undergo IMPT
Other Name: IMPT

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: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic resonance imaging (procedure)

Procedure: Modified Barium Swallow Study
Undergo MBSS
Other Names:
  • MBS
  • Modified Barium Swallow
  • VFSS
  • Videofluoroscopic Swallowing Study

Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • Positron emission tomography (procedure)

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Evaluation of return to work [ Time Frame: Up to 5 years ]
    Will be assessed by 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.

  16. 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.

  17. 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.

  18. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PRE-REGISTRATION (optional): Provide written informed consent
  • Age >= 18 years
  • Histological confirmation of p16+ OPSCC or HPV(+) OPSCC
  • 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), ENE, perineural invasion (PNI), positive margin, will go off study and be observed per current clinical standard of care
    • 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. 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 p16+ or HPV+ neck adenopathy can be registered to go on study. Should after primary resection, no primary tumor be identified, the patient will go off study and be treated per institutional standard of care
    • All treatment primarily, including surgery and chemotherapy will be performed at the enrolling institution

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05541016


Locations
Layout table for location information
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: Samir H. Patel, M.D.         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: Adam L. Holtzman, M.D.         
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015    mayocliniccancerstudies@mayo.edu   
Principal Investigator: David M. Routman, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Layout table for investigator information
Principal Investigator: David M, Routman, M.D. Mayo Clinic in Rochester
Additional Information:
Layout table for additonal information
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT05541016    
Other Study ID Numbers: GMROR2271
NCI-2022-06932 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
22-004443 ( Other Identifier: Mayo Clinic in Rochester )
DART 2.0 ( Other Identifier: Mayo Clinic in Rochester )
First Posted: September 15, 2022    Key Record Dates
Last Update Posted: January 17, 2024
Last Verified: January 2024

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action