Shorter radiation after trans-oral robotic surgery for HPV-related oropharyngeal cancer
Radiation Therapy in Reduced Dose and Hypofractionated Schedule After Trans-Oral Robotic Surgery in Intermediate Risk HPV-Mediated Oropharyngeal Squamous Cell Carcinoma
This trial tests whether giving a shorter course of radiation after trans-oral robotic surgery helps people with HPV-related oropharyngeal cancer have better quality of life.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 42 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of Utah Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 1 site (Salt Lake City, Utah) |
| Trial ID | NCT07044635 on ClinicalTrials.gov |
What this trial studies
This Phase 2 interventional study enrolls adults with p16/HPV-positive oropharyngeal squamous cell carcinoma who are eligible for trans-oral robotic surgery. After surgery, participants receive a shortened course of postoperative radiation therapy and are followed for functional outcomes, toxicities, and cancer control. Eligibility requires pre-operative TTMV-HPV DNA testing planned or collected and standard pathology including p16/HPV status, with ECOG performance status ≤2. The main goal is to see if shorter radiation reduces side effects and improves patient-reported quality of life without compromising oncologic outcomes.
Who should consider this trial
Good fit: Adults (≥18 years) with p16/HPV-positive oropharyngeal squamous cell carcinoma who are eligible for trans-oral robotic surgery, have ECOG ≤2, and have pre-operative TTMV-HPV DNA testing planned or collected are ideal candidates.
Not a fit: Patients with HPV-negative tumors, those not candidates for trans-oral robotic surgery, or those with poor performance status (ECOG >2) are unlikely to be eligible or to gain benefit from this shortened radiation approach.
Why it matters
Potential benefit: If successful, this approach could reduce radiation-related side effects and improve swallowing, speech, and overall quality of life for patients.
How similar studies have performed: Other de-escalation trials for HPV-positive oropharyngeal cancer have shown promising results in reducing treatment intensity while maintaining control in selected patients, though approaches and outcomes have varied across studies.
Eligibility criteria
Show full inclusion / exclusion criteria
Step 1 Registration: Pre-Operative Eligibility
Inclusion Criteria:
* Participant aged ≥ 18 years.
* Diagnosis of oropharyngeal squamous cell carcinoma.
* Eligible to receive transoral robotic surgery.
* If status is known, p16 positivity or HPV positivity by in situ hybridization on pathological sampling of lymph node or primary oropharyngeal tumor. If status not known at the time of step-1 registration, otherwise eligible participants may be enrolled and HPV/p16 status must be determined prior to step-2 registration.
* Pre-operative TTMV-HPV DNA test collected or is planned to be collected. Pre-operative TTMV-HPV DNA may be collected anytime up until the day of surgery as long as it is prior to surgery.
* Standard of care tests completed within 60 days of registration may be used for screening.
* Tests results are not required to confirm eligibility for step 1 registration.
* ECOG Performance Status ≤ 2
* Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Exclusion Criteria:
* History of prior mucosal head and neck cancer treated with radiation therapy
* Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this study
* Participant has smoked cigarettes within 1 month of registration
* Prior systemic anti-cancer therapy or any investigational therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter.
* Known distant metastatic disease.
* Current evidence of any condition that would, in the Investigator's judgment, contraindicate the participant's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[participants may not receive the drug through a feeding tube\], social/ psychological issues, etc.)
* Medical, psychiatric, cognitive, or other conditions that may compromise the participant's ability to understand the participant information, give informed consent, comply with the study protocol or complete the study.
Step 2 Registration - Experimental Arm
Inclusion Criteria:
* Completion of trans-oral robotic surgery.
* Pre- and post-operative TTMV-HPV DNA test results obtained.
* P16 positivity or HPV positivity by in situ hybridization on pathological sampling of lymph node or primary oropharyngeal tumor
* For participants of childbearing potential: Negative pregnancy test or evidence of permanent surgical sterilization. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* \< 50 years of age:
* Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
* Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
* ≥ 50 years of age:
* Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
* Had radiation-induced menopause with last menses \>1 year ago; or
* Had chemotherapy-induced menopause with last menses \>1 year
* Participants of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.5.2.
Exclusion Criteria:
* Meets ALL of the following criteria for low-risk disease (Note: participants may meet some without being excluded):
* Pre-operative TTMV-HPV DNA positive
* Post-operative TTMV-HPV DNA negative
* Disease: pT1 with ≤ 1 lymph nodes OR pT2N0
* \<10 pack year smoking
* No extranodal extension
* Negative surgical margins
* No perineural invasion
* No lymphovascular invasion
* Meets ANY of the following criteria for high-risk:
* Post-operative TTMV-HPV DNA positive
* Surgical margin positive --\>1 mm extranodal extension --≥ 5 lymph nodes
* Current evidence of any condition that would, in the Investigator's judgment, contraindicate the participant's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[participants may not receive the drug through a feeding tube\], social/ psychological issues, etc.)
Step 2 Registration - Exploratory Arm Inclusion Criteria
* Completion of trans-oral robotic surgery.
* Pre- and post-operative TTMV-HPV DNA test results obtained.
* Meets ANY of the following criteria:
* Post-operative TTMV-HPV DNA positive or indeterminate
* Surgical margin positive
* \>1 mm extranodal extension
* ≥5 lymph nodes
* Pre-operative TTMV-HPV DNA score of ≤ 50
* For participants of child bearing potential: Negative pregnancy test or evidence of permanent surgical sterilization. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
* \< 50 years of age:
* Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
* Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
* ≥ 50 years of age:
* Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
* Had radiation-induced menopause with last menses \>1 year ago; or
* Had chemotherapy-induced menopause with last menses \>1 year
* Participants of childbearing potential must agree to use a highly effective method of contraception as described in Section 5.5.2.
Exclusion Criteria
* Pre-operative TTMV-HPV DNA score of \> 50.
* Current evidence of any condition that would, in the Investigator's judgment, contraindicate the participant's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[participants may not receive the drug through a feeding tube\], social/ psychological issues, etc.).
Where this trial is running
Salt Lake City, Utah
- Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States (Recruiting)
Study contacts
- Study coordinator: Rachel Kingford
- Email: rachel.kingsford@hci.utah.edu
- Phone: 8015850115
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.