Detection of Minimal Residual Disease Based on HPV ctDNA in Cervical Cancer

Clinical Value of Minimal Residual Disease Detection Based on Human Papillomavirus Circulating Tumor DNA (HPV ctDNA) in Cervical Cancer

In this study, a large-scale cohort of cervical cancer patients was established in multiple centers. Minimal residual disease(MRD) was assessed by ddPCR detection of HPV E7 gene ctDNA to assess tumor burden and predict the risk of disease recurrence, so as to provide new biomarkers for precise treatment of cervical cancer patients. The study continued until 36 months after the end of treatment.

Study Overview

• Status: Recruiting
• Conditions: Uterine Cervical Neoplasms
• Intervention / Treatment: Other: detect HPV E7 ctDNA

Detailed Description

The purpose of this study is to assess MRD by detecting HPV E7 gene ctDNA to assess tumor burden and predict the risk of disease recurrence. According to the treatment methods, the patients were divided into two groups :(1) initial surgical treatment group (2) initial concurrent chemoradiotherapy group.

After the patients were enrolled in the study according to the criteria, they were given standard treatment. The patients were followed up every 3~6 months within 2 years after treatment and every 6~12 months from 3 to 5 years after treatment, including general and gynecological physical examination, cervical or vaginal cytology test, HPV typing test, SCC, CA125, and imaging examination such as CT or MRI if necessary.

Peripheral blood samples were collected to detect HPV E7 ctDNA before treatment, after treatment, and at 6, 12, 18, 24, 30, and 36 months of follow-up.

The primary endpoint is Disease-free survival (DFS, time from the treatment initiation to disease progression). Secondary endpoints include HPV ctDNA state before treatment, dynamic change trend of HPV ctDNA after treatment and overall survival (OS, time from the treatment initiation to death).

• Study Type: Observational
• Enrollment (Anticipated): 350

Contacts and Locations

• Study Contact: Name: Yang Xiang; Phone Number: 010-69156068; Email: XiangY@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Yang Xiang; Phone Number: 01069156068; Email: XiangY@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Cohort A: Patients with cervical cancer who were initially treated with surgery in Peking Union Medical College Hospital, Peking University Cancer Hospital and Beijing Obstetrics and Gynecology Hospital, capital Medical University were enrolled in this study.

Cohort B: Patients who were initially treated with concurrent chemoradiotherapy in Peking Union Medical College Hospital, Peking University Cancer Hospital and Beijing Obstetrics and Gynecology Hospital, capital Medical University were enrolled in this study.

Description

Inclusion Criteria:

• Pathological diagnosis: cervical squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma
• FIGO stage: IA2-IVA
• HPV typing: type 16 or 18
• ECOG 2-0
• The initial treatment was surgery (Cohort A) / concurrent chemoradiotherapy (Cohort B)

Exclusion Criteria:

• The diagnosis of cervical cancer was made within 3 years of other malignancies
• Pregnant or lactating women
• Refused to sign a consent form

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
initial surgical treatment group; After the patients were enrolled in the study according to the criteria, they were given standard treatment. The patients were followed up every 3~6 months within 2 years after treatment and every 6~12 months from 3 to 5 years after treatment, including general and gynecological physical examination, cervical or vaginal cytology test, HPV typing test, SCC, CA125, and imaging examination such as CT or MRI if necessary. Peripheral blood samples were collected to detect HPV E7 ctDNA before treatment, 2 weeks after surgery, (1 month after adjuvent radiotherapy if available) and at 6, 12, 18, 24, 30, and 36 months of follow-up.	Other: detect HPV E7 ctDNA; Peripheral blood was collected from the patients, and the copy number of HPV E7 gene in ctDNA was accurately detected by ddPCR
initial concurrent chemoradiotherapy group; After the patients were enrolled in the study according to the criteria, they were given standard treatment. The patients were followed up every 3~6 months within 2 years after treatment and every 6~12 months from 3 to 5 years after treatment, including general and gynecological physical examination, cervical or vaginal cytology test, HPV typing test, SCC, CA125, and imaging examination such as CT or MRI if necessary. Peripheral blood samples were collected to detect HPV E7 ctDNA before treatment, 1 month after radiotherapy and at 6, 12, 18, 24, 30, and 36 months of follow-up.	Other: detect HPV E7 ctDNA; Peripheral blood was collected from the patients, and the copy number of HPV E7 gene in ctDNA was accurately detected by ddPCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	time from the treatment initiation to disease progression	up to three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HPV ctDNA state before treatment	Peripheral blood was collected from the patients before treatment (surgery or chemotherapy), and the copy number of HPV E7 gene in ctDNA was accurately detected by ddPCR	up to three years
Dynamic change trend of HPV ctDNA after treatment	Peripheral blood was collected from the patients after treatment ((2 weeks after surgery), 1 month after radiotherapy and at 6, 12, 18, 24, 30, and 36 months of follow-up), and the copy number of HPV E7 gene in ctDNA was accurately detected by ddPCR	up to three years
Overall Survival	time from the treatment initiation to death	up to three years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Peking University Cancer Hospital & Institute; Beijing Obstetrics and Gynecology Hospital; Precision Scientific (Beijing) Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2025

Study Registration Dates

• First Submitted: September 4, 2022
• First Submitted That Met QC Criteria: September 4, 2022
• First Posted (Actual): September 8, 2022

Study Record Updates

• Last Update Posted (Actual): October 13, 2022
• Last Update Submitted That Met QC Criteria: October 11, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Neoplastic Processes; Uterine Cervical Neoplasms; Neoplasm, Residual
• Other Study ID Numbers: CC-MRD-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No