Biomarker-Driven Radiation Therapy Dose Reduction After Transoral Robotic Surgery for the Treatment of HPV-Positive Oropharyngeal Cancer

NCT05387915 | Active Not Recruiting Phase 2 DMC

• 4 other identifiers: STUDY00004187NCI-2022-02855WINSHIP5566-22P30CA138292
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial tests whether reduced dose radiation therapy after transoral robotic surgery works in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer. HPV positive oropharyngeal cancer has a better prognosis than oropharyngeal cancer not caused by HPV. A standard of care treatment for HPV positive oropharyngeal cancer is transoral robotic surgery followed by radiation therapy. However, this treatment is associated with many long-term side effects including difficulty swallowing. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving reduced dose radiation therapy after transoral robotic surgery may improve swallowing outcomes and quality of life compared to standard of care dose radiation therapy after transoral robotic surgery.

Conditions

Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8; Oropharyngeal HPV-Positive Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Swallowing Function Mean

  Will be assessed by the MD Anderson Dysphagia Index (MDADI) composite score (range 20 - 100, higher is better). Mean MDADI composite score will be reported at one year, along with a 95% confidence interval for the mean.

  At 1 year post surgery

• Swallowing Function T-Test

  A one-sample t-test will be conducted to compare the 1-year MDADI composite score with the null value of 79.1.

  At 1 year post surgery

Secondary Outcomes (7)

• Progression-Free Survival (PFS)

  From study entry to the earliest disease progression or death from any cause, assessed up to 24 months

• Overall Survival (OS)

  From study entry to death due to any cause, assessed up to 24 months

• Locoregional Control (LRC)- Six Month

  At 6 months

• Locoregional Control (LRC)- Two Year

  At 2 years

• Quality of Life (QoL) - MD Anderson Symptom Inventory

  At 2 years

Study Arms (1)

Treatment (reduced dose radiation therapy)

EXPERIMENTAL

Patients who are ctHPVDNA negative after surgery undergo reduced dose radiation therapy for 3 weeks (15 treatments). Patients who are ctHPVDNA positive after surgery undergo standard of care radiation therapy.

Radiation: Radiation Therapy

Interventions

Radiation Therapy RADIATION

Undergo reduced dose radiation therapy

Also known as: Cancer Radiotherapy, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (reduced dose radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%).
• Life expectancy \> 12 weeks as determined by the Investigator.
• Has diagnosis of HPV-associated squamous cell carcinoma of the oropharynx
• HPV positive either via p16 status or via in situ hybridization
• This includes patients with HPV positive squamous cell carcinoma of an unknown primary of the head and neck presumed to be of oropharyngeal origin who have undergone ipsilateral palatine and lingual tonsillectomies.
• pT1-2, pN0-1, cM0 disease.
• Positive ctHPVDNA titer prior to surgery.
• =\< 10 pack-year smoking history.
• Completed transoral robotic surgery (TORS) oropharyngectomy and at least ipsilateral neck dissection by an Emory otolaryngologist.
• Pathology must demonstrate at least one of the follow intermediate risk factors:
• Close margin (1 - 4 mm)
• Perineural invasion
• Lymphovascular space invasion
• positive lymph nodes without extranodal extension (ENE)

You may not qualify if:

• Patients with a prior history of malignancy in the last two years (excluding non- melanomatous skin cancer).
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier (i.e., have residual toxicities \> grade 1).
• Patients who are receiving any other investigational agents or an investigational device within 21 days before administration of first dose of study drugs.
• 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.
• Significant cardiovascular disease (e.g., myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 3 months prior to start of study therapy; angina requiring therapy; symptomatic peripheral vascular disease; New York Heart Association class 3 or 4 congestive heart failure; or uncontrolled grade \>= 3 hypertension (diastolic blood pressure \>= 100 mmHg or systolic blood pressure \>= 160 mmHg) despite antihypertensive therapy.

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Emory University Midtown Hospital

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Study Officials

• James E Bates, MD

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 24, 2022
• Study Start: June 6, 2022
• Primary Completion: January 5, 2026
• Study Completion (Estimated): January 5, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (3)