Circulating Tumour DNA and Urine Tumor DNA Detection of Minimal Residual Disease in Locally Advanced Upper Tract Urothelial Carcinoma With Radical Nephroureterectomy: A Cohort Study

In our study, the ultra-deep sequencing of circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) were performed to assess whether ctDNA and utDNA can be used as predictive biomarkers for the detection of minimal residual disease (MRD) and early diagnosis of UTUC recurrence, and explored the role of ctDNA and utDNA detection of MRD in the prediction of adjuvant therapy efficacy and prognostic evaluation.

Study Overview

• Status: Recruiting
• Conditions: Muscle Invasive Upper Tract Urothelial Carcinoma
• Intervention / Treatment: Drug: Adjuvant chemotherapy; Drug: adjuvant immunotherapy

Detailed Description

60% of Upper Urinary Tract Urothelial Carcinoma (UTUC) patients with muscle-invasive disease at diagnosis, which progresses rapidly, aggressively, and has a poor prognosis. Up to 30-40% of the patients may develop bladder recurrance after radical nephroureterectomy for primary upper tract urothelial carcinoma.

Minimal residual disease (MRD) refers to the small number of malignant cells that remain after curative treatments (curative intent surgical resection, radiotherapy, and/or chemotherapy). MRD is common in patients with blood cancer, and is known to be associated with recurrence and poor prognosis. Recent studies also reported that MRD-negative in postoperative solid tumors such as colorectal/colon cancer and muscle-invasive bladder cancer is associated with better survival outcomes. However, the clinical values of MRD monitoring for adjuvant therapy in postoperative UTUC remain inadequate.

A total of 103 patients with stage II-IV UTUC will be recruited in this clinical trial. The following plasma samples, urine samples and tumor tissues will be collected from each patient including 1) preoperative plasma and urine samples; 2) surgical tissue samples; 3) plasma and urine samples 1 month after surgery; 4) plasma and urine samples during adjuvant therapy; and 5) plasma and urine samples after adjuvant therapy; 6) plasma and urine samples in follow-up. In addition, demographic and tumor characteristics of the patients will be collected for subsequent analysis, including age, sex, tumor stage, pathological stage, disease couse time, etc. Tumor tissues and matched peripheral blood were collected before treatment and WES was used ctDNA detection techniques. For each patient, we selected up to 30 clonal somatic mutations for personalized, tumor informed ctDNA assay design.Statistical analyses will be performed to analyze the survival outcomes and to explore the clinical value of MRD monitoring for adjuvant therapy in postoperative UTUC.

• Study Type: Observational
• Enrollment (Anticipated): 103

Contacts and Locations

• Study Contact: Name: jiwei huang, M.D; Phone Number: 8613651682825; Email: huangjiwei@renji.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • RenJi Hospital
      • Contact: jiwei huang, M.D; Phone Number: 8621-68383716; Email: huangjiwei@renji.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

pathological comfirmed T2-4 or N+ and M0 upper tract urothelial carcinoma patients who received adjuvant chemotherapy or immunotherapy after radical nephroureterectomy

Description

Inclusion Criteria:

• pathological comfirmed T2-4 or N+ and M0 upper tract urothelial carcinoma
• Male or female aged ≥18 years old who are willing to sign the informed consent form
• have no distant metastasis
• have an ECOG 0 to 2
• upper tract urothelial carcinoma patients received radical nephroureterectomy
• have no multiple primary carcinoma received adjuvant chemotherapy or immunotherapy after surgery

Exclusion Criteria:

• • a prior history of bladder or synchronous bladder cancer

  • Pregnant or lactating women, or patients who are fertile but do not take contraceptive measures;
  • Severe infection;
  • Severe heart disease;
  • Uncontrollable neurological or mental disorders;
  • Severe diabetes mellitus;
  • Patients with severe autoimmune diseases.

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
adjuvant chemotherapy group; muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant chemotherapy	Drug: Adjuvant chemotherapy; cisplatin/carboplatin-gemcitabine 4-6 cycles
adjuvant immunotherapy group; muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant immunotherapy	Drug: adjuvant immunotherapy; immunotherapy for one year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year recurrence free survival	2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The predictive value of ctDNA and utDNA	2 year

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: Peking University First Hospital; Xiangya Hospital of Central South University; Fudan University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; West China Hospital; First Affiliated Hospital Xi'an Jiaotong University; Shanghai 10th People's Hospital; Ruijin Hospital; The First Affiliated Hospital of Soochow University; Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Tianjin Medical University Second Hospital; The Affiliated Hospital of Medical School of Ningbo University; Yantai Yuhuangding Hospital; The Second Affiliated Hospital of Dalian Medical University; Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology; Nanjing Medical University Affiliated Cancer Hospital; The First Affiliated Hospital, Zhejiang University School of Medicine; Lihuili Hospital; The Affiliated Drum Tower Hospital of Nanjing University Medical School; Zhongda Hospital Affiliated to Southeast University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: October 22, 2022
• First Submitted That Met QC Criteria: October 22, 2022
• First Posted (Actual): October 27, 2022

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 30, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Circulating tumor DNA; Minimal residual disease; upper tract urothelial carcinoma; Urine tumor DNA
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Carcinoma; Carcinoma, Transitional Cell; Neoplasm, Residual
• Other Study ID Numbers: UTUC-ADJ-MDR trial

Drug and device information, study documents

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