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

NCT ID: NCT06257017

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-02
• Study Completion Date: 2025-12-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine plus cisplatin chemotherapy arm (GC arm)

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

Group Type: EXPERIMENTAL

gemcitabine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Standard management arm (SM arm)

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

Group Type: OTHER

gemcitabine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Interventions

gemcitabine

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. aged 18-70 years old;

2. a score of ≤1 for the Eastern Cooperative Oncology Group (ECOG) Performance Status;

3. receiving radical cystectomy (with lymph node dissection) or nephroureterectomy;

4. histologically confirmed (surgical specimen) muscle invasive urothelial carcinoma, and the major histological type should be transitional cell carcinoma;

5. Classification of tumour, node and metastasis (TNM): pT2-4a N0-2M0;

6. 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;

7. 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
• Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)

8. able to understand and provide written informed consent, and agree to receive the treatment arrangement and study procedures stated in the informed consent

Exclusion Criteria

1. receiving any approved anti-cancer treatment within 3 weeks prior to study enrolment;

2. participation in another clinical trial with therapeutic intent within 28 days prior to enrolment;

3. suffering from malignancies other than urothelial carcinoma within 5 years prior to study enrolment;

4. conditions that contraindicate chemotherapy, such as renal impairment with creatinine clearance rate (CCr) <50 mL/min, hearing impairment, and inadequate marrow function;

5. anaphylactic or hypersensitivity reactions or other contraindication to cisplatin and gemcitabine;

6. active or uncontrolled infections, including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or tuberculosis;

7. pregnancy or breastfeeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pamela Youde Nethersole Eastern Hospital

OTHER

Sponsor Role: collaborator

Queen Mary Hospital, Hong Kong

OTHER

Sponsor Role: collaborator

Yung NA

OTHER

Sponsor Role: lead

Responsible Party

Yung NA

Clinical Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Yung Na, PHD

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

Queen Mary Hospital

Hong Kong, Hong Kong, Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Research Assistant

Role: CONTACT

stac@hku.hk

22554852

Facility Contacts

Research Assistant

Role: primary

stac@hku.hk

22554852

References

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.

Reference Type: DERIVED

PMID: 40857715 (View on PubMed)

Other Identifiers

HKURO202401

Identifier Type: -

Identifier Source: org_study_id