Surveillance of the Genetic Signature in Circulating Tumor DNA for Guiding Adjuvant Chemotherapy in Urothelial Carcinoma: A Pilot Randomized Controlled Trial

Trial Title: Surveillance of the Genetic Signature in Circulating Tumor DNA for Guiding Adjuvant Chemotherapy in Urothelial Carcinoma: A Pilot Randomized Controlled Trial

NCT ID: NCT06257017

Condition: Muscle Invasive Bladder Urothelial Carcinoma
Muscle-Invasive Bladder Carcinoma

Conditions: Official terms:
Carcinoma
Carcinoma, Transitional Cell
Urinary Bladder Neoplasms
Gemcitabine

Conditions: Keywords:
circulating tumor DNA
ctDNA
molecular residual disease

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: gemcitabine
Description: 1,000 mg/m2 intravenous gemcitabine on day 1 and day 8
Arm group label: Gemcitabine plus cisplatin chemotherapy arm (GC arm)
Arm group label: Standard management arm (SM arm)

Intervention type: Drug
Intervention name: Cisplatin
Description: 70 mg/m2 intravenous cisplatin (split into 2 doses on day 1 and day 8)
Arm group label: Gemcitabine plus cisplatin chemotherapy arm (GC arm)
Arm group label: Standard management arm (SM arm)

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.

Criteria for 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.

Gender: All

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: Queen Mary Hospital

Address:
City: Hong Kong
Country: Hong Kong

Status: Recruiting

Contact:
Last name: Research Assistant

Phone: 22554852
Email: stac@hku.hk

Investigator:
Last name: Yung Na, PHD
Email: Principal Investigator

Start date: February 2, 2024

Completion date: September 30, 2025

Lead sponsor:
Agency: Yung NA
Agency class: Other

Collaborator:
Agency: Pamela Youde Nethersole Eastern Hospital
Agency class: Other

Collaborator:
Agency: Queen Mary Hospital, Hong Kong
Agency class: Other

Source: The University of Hong Kong

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06257017