NCT04883281

Brief Summary

Varian Medical Systems has recently deployed a completely novel radiation treatment system called EthosTM, a first-of-its-kind system that allows for daily adapative radiotherapy (DART), such that the treatment for that day can be created on-the-fly based on the patient's current positioning and anatomy. This system is commercially-available and FDA-approved, and UTSW Radiation Oncology has installed two such units. The ability to adjust the dose delivery every day means both that adaptive therapy is possible with every fraction and that the PTV margin can be dramatically reduced/eliminated, since investigators are treating for that day's patient setup. Investigators are therefore proposing a randomized trial using DART with near marginless (ML) setup margins (a 1 mm margin will be retained for intrafractional motion).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P50-P75 for phase_2 head-and-neck-cancer

Timeline
Completed

Started Feb 2022

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 27, 2021

Completed
15 days until next milestone

First Posted

Study publicly available on registry

May 12, 2021

Completed
10 months until next milestone

Study Start

First participant enrolled

February 23, 2022

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 4, 2024

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 11, 2026

Completed
Last Updated

March 18, 2026

Status Verified

September 1, 2024

Enrollment Period

2.5 years

First QC Date

April 27, 2021

Last Update Submit

March 16, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Xerostomia Questionnaire (XQ)

    1-year score on the Xerostomia Questionnaire (XQ) to determine the difference in chronic xerostomia between patients treated with conventional INRT versus ML DART INRT. The XQ score at one year will be compared between the arms using a two-sided t test.

    1 year

Secondary Outcomes (3)

  • Development of acute and chronic toxicity in patients treated with and without DART

    1 year

  • Risk of locoregional recurrence with and without DART

    1 year

  • Patient reported outcomes

    1 year

Study Arms (2)

Involved Nodal Radiotherapy with conventional margins w or w/o chemotherapy

ACTIVE COMPARATOR

If a patient loses a significant amount of weight on treatment, or the tumor contour changes substantially, repeat CT simulation and re-planning is allowed in the CM arm. However, the gross tumor volume may not be reduced due to tumor shrinkage. The original extent of disease must be included in the replanned GTV.

Radiation: Intensity modulated radiation therapy (IMRT) with or without chemotherapyDrug: cisplatin, cetuximab, or carboplatin-paclitaxel

Involved Nodal Radiotherapy with marginless Daily Adaptive Radiotherapy w or w/o chemotherapy

EXPERIMENTAL

Patients in the ML/DART Arm will have their radiation plan adapted with every fraction. The adaptation process will be performed automatically on the Varian Ethos adaptive therapy software under the supervision of the treating physician.

Radiation: Intensity modulated radiation therapy (IMRT) with or without chemotherapyDrug: cisplatin, cetuximab, or carboplatin-paclitaxel

Interventions

Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel)

Involved Nodal Radiotherapy with conventional margins w or w/o chemotherapyInvolved Nodal Radiotherapy with marginless Daily Adaptive Radiotherapy w or w/o chemotherapy

chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel)

Involved Nodal Radiotherapy with conventional margins w or w/o chemotherapyInvolved Nodal Radiotherapy with marginless Daily Adaptive Radiotherapy w or w/o chemotherapy

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx, larynx, or hypopharynx. Squamous cell carcinoma of unknown primary is not allowed.
  • Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Diagnostic lymph node excision (\< 2 nodes) is also allowable.
  • Patients may undergo a diagnostic or therapeutic transoral resection for a T1-2 tonsil or base of tongue cancer.
  • Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded
  • Age ≥ 18 years.
  • ECOG Performance Status 0-2
  • Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential.
  • Neck CT and/or neck MRI, and PET-CT (at least skull-to-thigh).
  • Ability to understand and the willingness to sign a written informed consent.
  • All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

You may not qualify if:

  • Distant metastasis.
  • Inability to undergo PET-CT.
  • Stage I and II glottic carcinoma.
  • Gross total excision of both the primary and nodal disease.
  • Synchronous non-skin cancer primaries outside of the oropharynx, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer; in the latter case, surgery may occur before or after treatment, provided all other eligibility criteria are met.
  • Prior invasive malignancy with an expected disease-free interval of less than 3 years.
  • Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields.
  • Subjects may not be receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary).
  • 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, in the opinion of the investigator, would limit compliance with study requirements
  • pregnant or nursing women
  • History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

  • Sher DJ, Avkshtol V, Lin MH, Wang J, Chen L, Liao CY, Hughes R, Domal S, Ahn C, Moon DH. Impact of daily adaptive head and neck radiotherapy on toxicity and quality of life: results of the DARTBOARD phase II randomized trial. J Natl Cancer Inst. 2025 Dec 1;117(12):2488-2494. doi: 10.1093/jnci/djaf232.

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Radiotherapy, Intensity-ModulatedCisplatinCetuximab

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasms

Intervention Hierarchy (Ancestors)

Radiotherapy, ConformalRadiotherapy, Computer-AssistedRadiotherapyTherapeuticsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

April 27, 2021

First Posted

May 12, 2021

Study Start

February 23, 2022

Primary Completion

September 4, 2024

Study Completion

March 11, 2026

Last Updated

March 18, 2026

Record last verified: 2024-09

Locations