Clinical trial NCT05595408: Circulating and Urine Tumor DNA Dynamics Predict Minimal Residual Disease and Guide Adjuvant Therapy in Locally Advanced Upper Tract Urothelial Carcinoma
Official title: Circulating and Urine Tumor DNA Dynamics Predict Minimal Residual Disease and Guide Adjuvant Therapy in Locally Advanced Upper Tract Urothelial Carcinoma: A Prospective Longitudinal Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Muscle Invasive Upper Tract Urothelial Carcinoma
Keywords: upper tract urothelial carcinoma
Minimal residual disease
Circulating tumor DNA
Urine tumor DNA
adjuvant chemotherapy
adjuvant immunotherapy
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2022-10-27
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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 within 3 months

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.
* No neoadjuvant therapy
* No bilateral UTUC
* Surveillance time ≤3 month
* \<2 postoperative MRD surveillance assessments

Primary outcomes:
measure: extravesical recurrence free survival
timeFrame: 2 year
Secondary outcomes:
measure: The predictive value of ctDNA and utDNA
timeFrame: 2 year
measure: intravesical recurrence free survival
timeFrame: 2 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital
state: Shanghai
Study officials:
References: