Surveillance of the Genetic Signature in Circulating Tumor DNA for Guiding Adjuvant Chemotherapy in Urothelial Carcinoma

NCT06257017 | Recruiting Phase 2

• 1 other identifier: HKURO202401
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Urothelial carcinomas are one of the most commonly diagnosed cancers worldwide. Postoperative patients carry a poor prognosis with an estimated five-year disease-specific survival rate of 50%. To improve overall survival and reduce the recurrent risk, chemotherapy is recommended as a standard of care. However, currently in Hong Kong, neoadjuvant (preoperational) chemotherapy and adjuvant (postoperative) chemotherapy are not commonly or regularly provided due to the concern of the potential harm from both physicians and patients. Recently, genetic signature from circulating tumor DNA (ctDNA) is emerging as a pivotal biomarker for detecting caner in early stage and molecular residual disease (MRD). With strengths of non-invasive and superior sensitivity, ctDNA is hopefully to serve as a cancer-agnostic surrogate analyte for risk stratification of tumor recurrence, thereby guiding individually tailored treatment. Therefore, this study is proposed to exploratively assess the benefit of ctDNA-guided approach for postoperative adjuvant therapy.

Conditions

Muscle Invasive Bladder Urothelial Carcinoma; Muscle-Invasive Bladder Carcinoma

Keywords

circulating tumor DNA; ctDNA; molecular residual disease

Outcome Measures

Primary Outcomes (1)

• the radiational disease-free survival (rDFS)

  1 year

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  1 year

• Overall Survival (OS)

  5 year

• ctDNA clearance rate in ctDNA(+) patients

  1 year

Study Arms (2)

Gemcitabine plus cisplatin chemotherapy arm (GC arm)

EXPERIMENTAL

Patients in this group will receive adjuvant chemotherapy of gemcitabine and cisplatin, prior to radiological progression

Drug: gemcitabine; Drug: Cisplatin

Standard management arm (SM arm)

OTHER

Patients in this group will receive chemotherapy of gemcitabine and cisplatin only after radiological progression is observed

Drug: gemcitabine; Drug: Cisplatin

Interventions

gemcitabine DRUG

1,000 mg/m2 intravenous gemcitabine on day 1 and day 8

Gemcitabine plus cisplatin chemotherapy arm (GC arm); Standard management arm (SM arm)

Cisplatin DRUG

70 mg/m2 intravenous cisplatin (split into 2 doses on day 1 and day 8)

Gemcitabine plus cisplatin chemotherapy arm (GC arm); Standard management arm (SM arm)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged 18-70 years old;
• a score of ≤1 for the Eastern Cooperative Oncology Group (ECOG) Performance Status;
• receiving radical cystectomy (with lymph node dissection) or nephroureterectomy;
• histologically confirmed (surgical specimen) muscle invasive urothelial carcinoma, and the major histological type should be transitional cell carcinoma;
• Classification of tumour, node and metastasis (TNM): pT2-4a N0-2M0;
• absence of microscopic (i.e., positive margin) or gross residual of the tumor (R0 resection) and absence of metastasis, confirmed by a negative CT or MRI scan of pelvis, abdomen and chest within 4 weeks prior to enrolment;
• adequate hematologic and end-organ function, defined by the following laboratory results obtained within 28 days prior to the first study treatment:
• ANC≥1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
• WBC counts \> 2500 cells/μL
• Lymphocyte count ≥ 300 cells/μL
• Platelet count ≥ 100,000 cells/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
• Hemoglobin ≥ 9.0 g/dL
• AST, ALT, and alkaline phosphatase ≤ 2.5 × the upper limit of normal (ULN),
• PTT ≤ 1.5 × ULN
• PT ≤ 1.5 × ULN or INR \< 1.7

You may not qualify if:

• receiving any approved anti-cancer treatment within 3 weeks prior to study enrolment;
• participation in another clinical trial with therapeutic intent within 28 days prior to enrolment;
• suffering from malignancies other than urothelial carcinoma within 5 years prior to study enrolment;
• conditions that contraindicate chemotherapy, such as renal impairment with creatinine clearance rate (CCr) \<50 mL/min, hearing impairment, and inadequate marrow function;
• anaphylactic or hypersensitivity reactions or other contraindication to cisplatin and gemcitabine;
• active or uncontrolled infections, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or tuberculosis;
• pregnancy or breastfeeding.

Sponsors & Collaborators

• Yung NA: lead
• Pamela Youde Nethersole Eastern Hospital: collaborator
• Queen Mary Hospital, Hong Kong: collaborator

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong, Hong Kong

RECRUITING

Related Publications (1)

• Zhan Y, Ruan X, Wu Y, Chun TTS, Yao C, Shi R, Liu J, Ali S, Ma R, Huang D, Gao Y, Xu Y, Chen L, Du Q, Ng AT, Li CWB, Xu D, Na R. Surveillance of the Genetic Signature in Circulating Tumor DNA for Guiding Adjuvant Chemotherapy in Urothelial Carcinoma: Protocol for a Pilot Randomized Controlled Trial. JMIR Res Protoc. 2025 Aug 26;14:e72597. doi: 10.2196/72597.

  PMID: 40857715 DERIVED

MeSH Terms

Interventions

Gemcitabine; Cisplatin

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Yung Na, PHD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Assistant

CONTACT

22554852; stac@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 13, 2024
• Study Start: February 2, 2024
• Primary Completion: September 30, 2025
• Study Completion: December 30, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)