Oropharynx Cancer, HPV-Related Carcinoma
Conditions
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.
Interventions
RADIATIONRadiation
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).
Standard of care therapy, weekly, with either Cisplatin or Carboplatin
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity of treatment based off of Adverse Events collected per CTCAE v5.0 | up 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
| Measure | Time frame | Description |
|---|---|---|
| Tumor size of multi-imagine modality directed RT boost | 4 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 |
| Pattern of HPV ctDNA biomarkers in blood | baseline 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. |
| Pattern of HPV ctDNA biomarkers in urine | baseline, 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. |
| Local regional recurrence free survival | up to 3 years from start of treatment | The study team will summarize the number of patients with recurrence free survival |
| Biomarker analysis from tumor tissue, to compile biomarker information | pretreatment 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 toxicity | up to 2 years | Pre- and mid treatment MRI and PET imaging metrics in the tumor will be correlated with 2 year PFS |
| Oral microbiome analysis to compile biomarker information | pre 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. |
Countries
United States
Outcome results
None listed