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

Phase 2
Active, not recruiting
Conditions
HPV-Related Carcinoma
Oropharynx Cancer
Interventions
Registration Number
NCT06234748
Lead Sponsor
University of Michigan Rogel Cancer Center
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
19
Inclusion Criteria
  • 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.
Exclusion Criteria
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  • 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;

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment ArmPlatinum based chemotherapyPatients 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.
Treatment ArmRadiationPatients 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.
Primary Outcome Measures
NameTimeMethod
Toxicity of treatment based off of Adverse Events collected per CTCAE v5.0up to 3 years from start of treatment

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.

Secondary Outcome Measures
NameTimeMethod
Pattern of HPV ctDNA biomarkers in bloodbaseline and surveillance, up to 24 months

The study team will summarize the distribution of candidate biomarkers descriptively at each timepoint and also summarize longitudinal change graphically.

Tumor size of multi-imagine modality directed RT boost4 weeks after starting treatment

The volume of tumor to be boosted will be calculated for each patient and summarized. Both physiologic MRI and FDG-PET will be used

Oral microbiome analysis to compile biomarker informationpre and post treatment, up to 24 months

The study team will summarize the distribution of candidate biomarkers descriptively at each timepoint and also summarize longitudinal change graphically.

Local regional recurrence free survivalup to 3 years from start of treatment

The study team will summarize the number of patients with recurrence free survival

Pattern of HPV ctDNA biomarkers in urinebaseline, treatment, and surveillance, up to 24 months

The study team will summarize the distribution of candidate biomarkers descriptively at each timepoint and also summarize longitudinal change graphically.

Biomarker analysis from tumor tissue, to compile biomarker informationpretreatment and at 2 weeks

The study team will summarize the distribution of candidate biomarkers descriptively at each timepoint and also summarize longitudinal change graphically.

MRIs and FDG PET scans- efficacy and toxicityup to 2 years

Pre- and mid treatment MRI and PET imaging metrics in the tumor will be correlated with 2 year PFS

Trial Locations

Locations (1)

University of Michigan Rogel Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

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