Recruiting

Phase 2

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

Sponsor:

Mayo Clinic

Code:

NCT05541016

Conditions

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

Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

Stage I Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Cisplatin

Computed Tomography

Diffusing Alpha-emitter Radiation Therapy

Docetaxel

Study Details

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.

Conditions

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

Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma

Stage I Oropharyngeal (p16-Negative) Carcinoma AJCC v8

Study ID

NCT05541016

Start date

Feb 21, 2023

Status verified date

May, 2026

Completion date

Aug 1, 2029

Anticipated

Primary completion date

Aug 1, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

455 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

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.

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.

Interventions

Biospecimen Collection

Undergo blood and saliva specimen collection for NavDx testing

Cisplatin

Given IV

Computed Tomography

Undergo CT scan

Diffusing Alpha-emitter Radiation Therapy

Undergo DART

Docetaxel

Given IV

Intensity-Modulated Proton Therapy

Undergo IMPT

Intensity-Modulated Radiation Therapy

Undergo IMRT

Magnetic Resonance Imaging

Undergo MRI

Modified Barium Swallow Study

Undergo MBSS

Observation Activity

Undergo observation

Positron Emission Tomography

Undergo PET scan

Quality-of-Life Assessment

Ancillary studies

Questionnaire

Ancillary studies

Primary outcome measure

Progression-free survival (PFS) [ Time Frame: From registration to the first of either disease progression/recurrence or death, assessed up to 5 years ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Arizona

Recruiting

Scottsdale, Arizona, United States, 85259

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Shelby Watkin

480-342-2000

Principal Investigator:

Samir H. Patel, M.D.

Mayo Clinic in Florida

Recruiting

Jacksonville, Florida, United States, 32224-9980

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Caroline Pamboukas

904-953-2791

Principal Investigator:

Adam L. Holtzman, M.D.

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

David M. Routman, M.D.

More Information

Sponsor

Mayo Clinic

Last update posted

May 12, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-05-12.