Using genetic signatures in blood to guide chemotherapy for bladder cancer

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

This study is testing if analyzing genetic markers in blood can help doctors choose the best chemotherapy for patients with muscle-invasive bladder cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: The University of Hong Kong (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Hong Kong, Hong Kong)
• Trial ID: NCT06257017 on ClinicalTrials.gov

What this trial studies

This study investigates the use of circulating tumor DNA (ctDNA) as a biomarker to guide adjuvant chemotherapy in patients with muscle-invasive bladder urothelial carcinoma. By analyzing the genetic signatures found in ctDNA, the study aims to improve risk stratification for tumor recurrence and tailor chemotherapy treatments accordingly. The approach is designed to be non-invasive and potentially more sensitive than traditional methods. Participants will receive standard chemotherapy agents, gemcitabine and cisplatin, based on their ctDNA results.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with muscle-invasive urothelial carcinoma who have undergone radical cystectomy and have no residual disease.

Not a fit: Patients with metastatic disease or those who have not undergone complete surgical resection may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more personalized and effective chemotherapy treatments for bladder cancer patients, potentially improving survival rates.

How similar studies have performed: Other studies have shown promise in using ctDNA for cancer detection and monitoring, suggesting this approach may be effective.

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.

Where this trial is running

Hong Kong, Hong Kong

• Queen Mary Hospital — Hong Kong, Hong Kong, Hong Kong (Recruiting)

Study contacts

• Principal investigator: Yung Na, PHD — The University of Hong Kong
• Study coordinator: Research Assistant

Conditions Muscle Invasive Bladder Urothelial Carcinoma; Muscle-Invasive Bladder Carcinoma; circulating tumor DNA; ctDNA; molecular residual disease