Trial of Individualized Adaptive RT in HPV-related High Risk Oropharynx Cancer

NCT06234748 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: UMCC 2023.006HUM00231890
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study seeks to study the population of HPV-related oropharynx cancer patients that appear to be at highest risk for treatment failure with loco-regional failure and distant metastases including cT4 or cN3. The study team aims to determine if it is feasible to use multi-modality imaging (both DCE MRI and FDG-PET) to optimize the radiation boost in high risk p16+ OPSCC with similar or decreased toxicity compared to historic standard therapy.

Conditions

Oropharynx Cancer; HPV-Related Carcinoma

Outcome Measures

Primary Outcomes (1)

• Toxicity of treatment based off of Adverse Events collected per CTCAE v5.0

  The study team will calculate rates of in-field RT related toxicities including Grade 4+ and Grade 3+ with associated confidence intervals including dysphagia, mucositis, oral pain and oral bleeding events.

  up to 3 years from start of treatment

Secondary Outcomes (7)

• Tumor size of multi-imagine modality directed RT boost

  4 weeks after starting treatment

• Local regional recurrence free survival

  up to 3 years from start of treatment

• Pattern of HPV ctDNA biomarkers in blood

  baseline and surveillance, up to 24 months

• Pattern of HPV ctDNA biomarkers in urine

  baseline, treatment, and surveillance, up to 24 months

• Oral microbiome analysis to compile biomarker information

  pre and post treatment, up to 24 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Patients will initially receive a single prescription of 70 Gy to PTVhigh in 35 fractions with RT given once daily, 5 days a week along with weekly platinum (standard therapy). All fields must be treated daily. On days when chemotherapy is given, it will be administered prior to RT. Prescription to high risk PTV will be 70Gy in 35 fractions and to PTV2 will be 56Gy in 35 fractions.

Radiation: Radiation; Drug: Platinum based chemotherapy

Interventions

Radiation RADIATION

Patients will undergo 2 phases of RT replanning: 1. Based on 2-week DCE-MRI low BV tumor subvolume, patients will have a PTVboost1 that will start to receive 2.5Gy/day with fraction 16. PTVboost1=(persistent lowBVsubvolume\_2 wks+ MTV3\_2 weeks)+ 3mm margin. 2. Based on 4-week FDG-PET MTV3, patients with have a PTVboost2 cone down that will receive 2.5Gy/day starting with fraction 23. PTVboost2=(LBV\_2 wks + MTV3\_4wks)+ 3mm margin 3. Thus, the tumor subvolumes that are included in the boost from fx16-35 will receive 86 Gy EQD2 (80Gy physical dose) and the FDG-avid subvolumes which start boost at 2 weeks but are not persistently avid at 4 wks will receive 76Gy EQD2 (74Gy physical dose).

Treatment Arm

Platinum based chemotherapy DRUG

Standard of care therapy, weekly, with either Cisplatin or Carboplatin

Also known as: Cisplatin, Carboplatin

Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically confirmed, locally/regionally advanced p16+ squamous cell carcinoma of the oropharynx referred for definitive chemo-RT
• AJCC 8 Stage III (cT4 or N3)
• ECOG 0-1 performance status within two weeks of enrollment
• Pre-treatment laboratory criteria within four weeks of enrolment: WBC \> 3500/ul, granulocyte \> 1500/ul. Platelet count \> 100,000/ul. Total Bilirubin \< 1.5 X ULN. AST and ALT \< 2.5 X ULN. Estimated Creatinine clearance \>30cc/min
• Patients must be able to receive protocol chemotherapy in the judgment of the treating Medical Oncologist
• Age \>18
• All patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines.
• Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study.

You may not qualify if:

• Patients should have no contraindications to having a contrast enhanced MRI scan. These contraindications will be assessed at the time of enrollment using the guidelines set up and in clinical use by the Institutional Standard Practice.
• Patients should have no contraindications to having a contrast enhanced PET scan. These contraindications will be assessed at the time of enrollment using the guidelines set up and in clinical use by the Institutional Standard Practice.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
• Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if \> 3 years prior to study;

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Radiation; Platinum Compounds; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Michelle Mierzwa

  University of Michigan Rogel Cancer Center

  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: SPONSOR

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: January 31, 2024
• Study Start: December 20, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: May 13, 2025

Record last verified: 2025-05

Locations

US (1)