Individualized Adaptive De-escalated Radiotherapy for HPV-related Oropharynx Cancer

A Multi-Center Phase II Trial of Individualized Adaptive De-escalated Radiotherapy Using Pre and Mid-Treatment FDG-PET/CT for HPV-related Oropharynx Cancer

This prospective study aims to utilize pre- and mid-treatment PET-CT to guide de-escalation of radiation therapy in HPV-related squamous cell carcinoma of the oropharynx.

Study Overview

• Status: Completed
• Conditions: Oropharynx Cancer
• Intervention / Treatment: Drug: Carboplatin; Radiation: Radiation Therapy; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital
    • Ann Arbor, Michigan, United States, 48109
      • VA Ann Arbor Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have FDG-avid and histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization.
• AJCC eighth edition staging stage 1 and stage 2
• Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
• History/physical examination, including documentation of weight within 4 weeks prior to registration;
• FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration;
• Zubrod Performance Status (A quantification of the functional status of cancer patients that runs from 0 to 5, with 0 denoting perfect health and 5 death) 0-1 within 4 weeks prior to registration;
• Age ≥ 18;
• Able to tolerate PET/CT imaging required to be performed
• CBC/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function;
• Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45 ml/min within 4 weeks prior to registration;
• 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.
• The patient must provide study-specific informed consent prior to study entry.

Exclusion Criteria:

• cT4, cN3 or cM1 disease
• "Matted nodes" as determined by review with Neuroradiology
• Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed.
• Carcinoma of the neck of unknown primary site origin (even if p16 positive);
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
• Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if > 3 years prior to study;
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
• Severe, active co-morbidity;
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception;
• Poorly controlled diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Treatment; Patients will receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy)	Drug: Carboplatin; AUC=1 weekly during radiation therapy. Carboplatin will be given once a week in combination with paclitaxel (standard treatment), concurrent with radiation therapy. Given IV.; Radiation: Radiation Therapy; Patients will initially receive a single prescription of 70 Gy to PTV1 in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). Dose will be reduced to 54Gy to high risk PTV and 43.2Gy to low risk PTV all in 27 fractions for patients who meet pPET-CT and iPET-CT parameters.; Drug: Paclitaxel; 30 mg/m2 weekly during radiation therapy. Paclitaxel will be given once a week in combination with carboplatin (standard treatment), concurrent with radiation therapy. Given IV.
Experimental: De-escalation Treatment; Patients will initially receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). If certain parameters are met radiation therapy will be reduced to 54Gy to high risk Planned Target Volume (PTV) and 43.2Gy to low risk PTV all in 27 fractions.	Drug: Carboplatin; AUC=1 weekly during radiation therapy. Carboplatin will be given once a week in combination with paclitaxel (standard treatment), concurrent with radiation therapy. Given IV.; Radiation: Radiation Therapy; Patients will initially receive a single prescription of 70 Gy to PTV1 in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). Dose will be reduced to 54Gy to high risk PTV and 43.2Gy to low risk PTV all in 27 fractions for patients who meet pPET-CT and iPET-CT parameters.; Drug: Paclitaxel; 30 mg/m2 weekly during radiation therapy. Paclitaxel will be given once a week in combination with carboplatin (standard treatment), concurrent with radiation therapy. Given IV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients With Local Regional Recurrence (LRR) of Disease	RECIST (Response Evaluation Criteria In Solid Tumors) will be used to evaluate response and recurrence. All patients will be analyzed together as the goal of the study is to estimate risk of LRR in this patient population treated with this particular strategy in which some patients continue to receive standard therapy while others are de-escalated. Results will also be estimated and reported separately for patients receiving standard or de-escalated therapy.	1 Year
Change in Metabolic Tumor Volume 50% (MTV 50%)	The change in metabolic tumor volume (MTV)50% at the mid-treatment timepoint will be calculated as percent change from baseline and used as a continuous variable in a Cox model for an outcome of time to LRR. Will also evaluate more non-parametrically, the relation between hazard of LRR and mid-treatment MTV50% using a kernel estimator in a Cox model.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Toxicity	Toxicity outcomes will be estimated as proportions of patients with available toxicity data at 3, 6 12 and 24 months.	3, 6, 12 and 24 Months
Quality of Life Assessed Per the Functional Assessment of Cancer Therapy-Head and Neck (FACTHN)	Quality of life (QOL) outcomes and swallowing study results will be summarized descriptively by timepoint. If there is substantial missingness in the QOL outcomes the study will assess for informative missingness by comparing earlier QOL scores and change in earlier QOL scores between patients missing QOL at later time points (e.g. 1 or 2 years).	2 Years
The Proportion of Patients Alive		2 Years
Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants	The proportion of patients in whom ctDNA is detectable will be summarized as a binomial proportion at each timepoint. Additionally, the relation between ctDNA presence or other characteristics and patient outcomes including time to local or distant progression will be assessed by including ctDNA as a covariate in Cox models for local or distant control.	4 weeks

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: National Cancer Institute (NCI); VA Ann Arbor Healthcare System
• Investigators: Principal Investigator: Michelle Mierzwa, M.D., University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Actual): May 5, 2023
• Study Completion (Actual): May 5, 2025

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (Actual): January 30, 2018

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Oropharyngeal Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: UMCC 2017.113; HUM00136258 (Other Identifier: University of Michigan); U01CA183848 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes