Risk-adapted Therapy in HPV+ Oropharyngeal Cancer Using Circulating Tumor (ct)HPV DNA Profile - The ReACT Study

Jonathan Schoenfeld, MD, MPH3 个研究点分布在 1 个国家目标入组 145 人开始时间: 2021年7月2日最近更新: 2026年8月5日

适应症

干预措施

试验速览

阶段: 2 期
状态: 招募中
发起方
入组人数: 145
试验地点: 3
主要终点: Progression Free Survival 2 Years

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This research is being conducted to understand if treatment can be tailored for participants with HPV-related oropharynx cancers using both clinical features (stage of the tumor, smoking status) combined with an investigational HPV blood test.

The names of the test and treatments involved in this study are:

NavDx® HPV ctDNA testing (HPV blood test)
Radiation therapy
Chemotherapy: Cisplatin, or Carboplatin and Paclitaxel (not all participants receive any or all of these agents)

详细描述

This research study involves HPV DNA testing (a blood test that measures the levels of DNA from the human papillomavirus in the bloodstream which investigator think sheds from the cancer itself), radiation therapy, and chemotherapy for some participants.

The research study procedures includes: screening for eligibility, and study treatments including evaluations and follow-up visits.

The names of the test and treatments involved in this study are:

NavDx® HPV ctDNA testing (HPV blood test)
Radiation therapy: Radiation therapy alone or combined with chemotherapy is considered a standard treatment for this disease. The investigators are researching the effectiveness of reducing the radiation doses and, in some cases, also reducing the chemotherapy dose for certain participants with favorable clinical characteristics and with certain HPV blood test results.
Chemotherapy: Cisplatin, or Carboplatin and Paclitaxel (not all participants receive any or all of these agents)
Study treatment will for up to 7 weeks and participants will be followed for 5 years from the beginning of the study.
It is expected that about 145 people will take part in this research study.

The HPV ctDNA levels will be measured using a blood test called NavDx®, which will be provided free of charge from the company NAVERIS. ctDNA testing refers to circulating tumor (ct)DNA or measuring DNA fragments floating in the bloodstream that are released from the cancer cells. This testing has shown promise in early detection of cancer recurrence in several solid tumor types (including colorectal, urothelial, and breast cancer). Additionally, recent studies have shown a connection between baseline ctDNA levels and disease risk.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 22 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Participants must meet the following eligibility criteria at the time of screening to be eligible to participate in the study:
•Subject must have histologically or cytologically confirmed, stage I, II, or III (N3 disease excluded), HPV associated oropharyngeal (tongue base or tonsil) squamous cell carcinoma, as defined by 2017 American Joint Committee on Cancer (AJCC), 8th edition staging.
•-- Patients with HPV-associated disease of unknown primary (cT0) are eligible
•HPV status should be confirmed on tissue biopsy or cytologic sample by any of the following:
•Immunohistochemical staining for p16 with ≥70% expression
•Confirmatory DNA testing (PCR or ISH) for high-risk subtype
•Willing to provide blood and tissue from a diagnostic biopsy and blood samples before, during, and after treatment.
•Detectable HPV ctDNA blood sample at baseline, prior to treatment, using the NavDx® assay that detects HPV subtype 16
•Age 22 years or older
•ECOG performance status ≤ 2
•Participants should have adequate organ and marrow function if they are to receive chemotherapy (cisplatin, or carboplatin and paclitaxel) with radiation concurrently as determined by standard institutional guidelines and investigator preference (parameters suggested below).
•absolute neutrophil count (ANC) ≥ 1000
•platelet count ≥ 100,000
•total bilirubin of 1.5 or less
•creatinine of 1.6 or less (or a CrCl ≥50 mL/min) per institutional standards.
•Planning to receive non-surgical management for HPV+ oropharyngeal cancer
•Ability to understand and the willingness to sign a written informed consent document.
•Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of (chemo)radiation therapy. "Women of childbearing potential (WOCBP)" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level above 40 mIU/mL.
•Men who are sexually active with WOCBP must agree to use any contraceptive method with a failure rate of less than 1% per year. Men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 1 month after treatment. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception.

排除标准

•Patients with AJCC 2017 8th edition stage IVC (metastatic) disease; or patients with fixed cervical nodal disease suggesting extranodal extension or N3 disease as suggested by lymph nodes measuring >6 cm.
•Subject who has had prior radiation and/or chemotherapy for head and neck cancer.
•Any history of oncologic surgical resection (transoral robotic surgery, TORS) or oncologic neck dissection prior to undergoing definitive RT or chemoradiation. Note: prior tonsillectomy as part of identification of the primary tumor site or biopsy and excisional nodal biopsy is/are acceptable provided the patient would be standardly treated to definitive treatment doses of therapy off protocol. Patients with HPV-associated unknown primary should not have undergone a neck dissection to be eligible.
•Undetectable baseline HPV ctDNA result by NavDx® testing or detectable baseline HPV ctDNA result for subtypes 18, 31, 33, or
•Pregnant or lactating women.
•Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
•Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and low risk prostate adenocarcinoma being managed with active surveillance. A history of another separate malignancy in remission without evidence of active disease is permitted if chance3 of recurrence is thought to be low.