Selective dose reduction of neck radiation in HPV-associated oropharyngeal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase II, single-arm study evaluating dose-de-escalation strategies in patients with HPV-positive oropharyngeal cancer treated with surgery followed by radiation or with primary radiation. The trial will test reduced radiation to contralateral neck lymph nodes (and other targeted reductions) with the goal of maintaining cancer control while lowering treatment-related toxicity. Circulating tumor DNA is also being used as a biomarker to monitor response. Participants will undergo standard care with modified radiation regimens, and outcomes will focus on safety, cancer control, and treatment-related side effects.

Why it matters

Who can join: the full rules

4.1 Step 1 Registration 4.1.1 Step 1 Inclusion

(Y) 1. Is there pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx or squamous cell carcinoma unknown primary? Note: specimen from cervical lymph nodes with a well-defined primary site documented clinically or radiologically is acceptable; in patients with carcinoma of unknown primary this will be sufficient for pathologic confirmation without a clinically or radiographically defined primary site.

(Y) 2. Is the patient ≥ 18 years of age?

(Y) 3. Did the patient provide study specific informed consent prior to study entry, including consent for mandatory submission of tissue for required p16 review?

(Y) 4. Clinical TNM staging criteria by cohort (AJCC 8th edition):

TORS candidate patients must be:

• cT0-4 and N0, N1, N3

Non-TORS candidate patients must be either:

* cT1-4 N0, N1, N3
* cT1-3 N2 with \< 10 pack years

4.1.2 Step 1 Exclusion

(N) 1. Patient who are clinical N2 and have ≥10 pack years smoking history

(N) 2. Patients who are clinical T4N2

(N) 3. Patients with distant metastasis (M1)

4.2 Step 2 Registration 4.2.1 Step 2 inclusion

(Y) 1. Does the patient have pathologically (histologically or cytologically) proven P16+ status?

(Y) 2. Does the patient have appropriate imaging (PET/CT preferred, CT neck with IV contrast and CT chest without contrast as recommended alternative to PET/CT) completed within 90 days of enrollment?

(Y) 3. Does the patient have clinical or pathological M0 staging? (Y) 4. Patients who have undergone TORS must have pathological stage pT1-4 N0, N1 or N3. TORS patients found to be clinical N2 post TORS or have contralteral neck dissection and positive nodes will be excluded.

(Y) 5. Is the patient a candidate for bilateral radiation based on evaluation by ENT, Rad Onc, or Med Onc and review at multi-disciplinary tumor board?

(Y) 6. Non-TORS patients who are cT1-3 N0, N1, N2 and have \<10 PY must have completed a ctDNA evaluation prior to Step 2 enrollment.

(Y) 7. Non-TORS patients who are cT1-3 N2 must have a positive ctDNA result prior to Step 2 enrollment.

(Y) 8. Was a general history and physical examination performed by a radiation oncologist, medical oncologist, or head and neck surgeon within 60 days prior to registration?

(Y) 9. Was the patient's Zubrod Performance Status 0-1 within 30 days prior to registration?

(Y) 10. If a woman of child-bearing potential or sexually active male, is the patient willing to use effective contraception throughout their participation in the treatment phase of the study and at least 180 days following the last study treatment.

4.2.2 Step 2 Exclusion

(N) 1. Does the patient have cancer considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), nasopharynx, hypopharynx, or larynx?

(N) 2. Does the patient have distant metastasis?

(N) 3. Does the patient have prior invasive malignancy (except non-melanomatous skin cancer and low/intermediate risk prostate cancer) unless disease free for a minimum of 3 years?

(N) 4. Did the patient have prior systemic chemotherapy for the study cancer (prior chemotherapy for a different cancer is allowable)?

(N) 5. Did the patient have prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields?

(N) 6. Did the patient have prior cancer-related surgeries of curative intent of the head and neck excluding superficial removal of cutaneous skin malignancies?

(N) 7. Does the patient have any co-morbid condition or concern that may interfere with follow up per experimental arm?

(N) 8. Does the patient have an active drug or alcohol dependency that in the opinion of the investigator would limit compliance with study requirements?

(N) 9. Is the patient pregnant or nursing (an exception will be made for nursing patients that are not receiving chemotherapy)?

Where it's running

• Maryland Proton Treatment Center
  Baltimore, Maryland, United States Recruiting
• University of Maryland Greenebaum Cancer Center
  Baltimore, Maryland, United States Recruiting
• Central Maryland Radiation Oncology
  Columbia, Maryland, United States Recruiting
• Baltimore Washington Medical Center- Tate Cancer Center
  Glen Burnie, Maryland, United States Recruiting

Study contacts

• Principal investigator: Jason K Molitoris — University of Maryland/Maryland Proton Treatment Center
• Study coordinator: Jason K Molitoris
• Email: jmolitoris@umm.edu
• Phone: 410-328-6080

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Neoadjuvant chemoimmunotherapy with PD-1 blockade to reduce surgery for advanced head and neck cancer

  This approach will try a short course of chemotherapy plus the PD-1 drug toripalimab before standard treatment for people with advanced head and neck cancers to shrink tumors and allow less extensive surgery or radiation.

  Recruiting Phase 2 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Baltimore, Maryland · NCT07209189

• Mild heat therapy added to standard treatment for locally advanced head and neck cancer

  This early-stage trial tests whether mild hyperthermia can be safely added to standard radiotherapy with or without chemotherapy for locally advanced head and neck cancer.

  Recruiting Phase 1 Erasmus Medical Center · Rotterdam, South Holland · NCT07690618

• Docetaxel and SX-682 in head and neck cancers and prostate cancer

  This trial tests a new drug SX-682 together with docetaxel in adults whose head and neck cancers or prostate cancer have returned or spread.

  Recruiting Phase 1/2 National Institutes of Health Clinical Center (CC) · Bethesda, Maryland · NCT07667400

• EPI-326 for EGFR-mutant non-small cell lung cancer and head and neck squamous cell carcinoma

  This phase 1 trial will try EPI-326, a new drug, in people with EGFR-mutant non‑small cell lung cancer or advanced head and neck squamous cell carcinoma to find safe doses, study how the body handles it, and look for early signs it shrinks tumors.

  Recruiting at 8 sites Phase 1 EpiBiologics · Los Angeles, California and 7 other locations · NCT07462377

• Personalized compartment-sparing postoperative radiation for head and neck cancer

  This trial tests whether targeted, compartment-sparing postoperative radiation can reduce side effects while keeping cancer control for people with surgically treated head and neck squamous cell carcinoma.

  Recruiting at 3 sites Phase 2 Insel Gruppe AG, University Hospital Bern · Basel and 2 other locations · NCT07058805

• New blood test to reduce radiation in HPV-related throat cancer treatment

  This study is testing a new blood test to see if it can help identify patients with HPV-related throat cancer who might not need radiation after surgery, aiming to reduce side effects while keeping survival rates high.

  Recruiting at 2 sites Phase 2 University of Maryland, Baltimore · Baltimore, Maryland and 4 other locations · NCT06088381

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.