Trastuzumab Rezetecan and Gemcitabine before surgery for HER2-positive UTUC

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2 interventional trial evaluates a neoadjuvant regimen combining a HER2-targeted antibody-drug conjugate with gemcitabine in patients with HER2 2+ to 3+ UTUC. Participants will receive a 21-day cycle of four neoadjuvant cycles, followed by up to two adjuvant cycles if pathological complete response is not achieved, prior to radical nephroureterectomy. Eligibility includes adults 18–75 with suitable renal function, adequate organ function, and confirmed HER2 expression, and tumor staging up to T4aN1M0. The study aims to assess the safety and preliminary efficacy of this approach in the perioperative setting.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. The subject voluntarily participates in the study, provides written informed consent, and is able to comply with study procedures and follow-up visits.
2. Aged between 18 and 75 years.
3. Patients diagnosed with upper tract urothelial carcinoma (UTUC) who are candidates for radical nephroureterectomy with bladder cuff excision.
4. Clinical stage T1N0M0 - T2-T4aN1M0 (evaluated by CT/MRI/PET-CT).
5. Histopathology confirms urothelial carcinoma as the predominant component; IHC testing shows HER2 expression of 2+ to 3+.
6. ECOG performance status ≤ 2.
7. Laboratory parameters meet all of the following criteria:

   * Absolute neutrophil count ≥ 1.5 × 10⁹/L
   * Platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 90 g/L
   * Total bilirubin ≤ 1.5 × ULN
   * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 2.5 × ULN; serum creatinine ≤ 3 × ULN
8. Cardiac function: New York Heart Association (NYHA) classification \< Grade III.

Exclusion Criteria:

1. Received live attenuated vaccines within 4 weeks prior to enrollment or plan to receive such vaccines during the study.
2. Received systemic chemotherapy, anti-PD-1/PD-L1 agents, or HER2-targeted therapy within the previous 6 months.
3. Known hypersensitivity to gemcitabine, Trastuzumab Rezetecan, or any of their excipients.
4. Active, known or suspected autoimmune disease.
5. Known history of primary immunodeficiency.
6. Known history of solid organ allotransplantation or allogeneic hematopoietic stem cell transplantation.
7. Female patients who are pregnant or breastfeeding.
8. Untreated acute or chronically active hepatitis B or hepatitis C infection. Patients receiving antiviral therapy may be considered eligible at the investigator's discretion with ongoing viral load monitoring.
9. Uncontrolled concurrent illnesses, including but not limited to:

   1. HIV infection (positive HIV antibody).
   2. Severe active infection with inadequate clinical control.
   3. Evidence of severe or uncontrolled systemic disease (e.g., severe psychiatric or neurological disorders, epilepsy or dementia; unstable or decompensated respiratory, cardiovascular, hepatic or renal disease; uncontrolled hypertension defined as CTCAE Grade ≥2 hypertension despite medical treatment).
10. Active bleeding, newly diagnosed thromboembolic disease requiring therapeutic anticoagulation, or bleeding diathesis.
11. Diagnosis of another malignant tumor within the past 5 years.
12. Active tuberculosis

Where it's running

• Huanggang Central Hospital
  Huanggang, Hubei, China Recruiting
• Jingzhou Central Hospital
  Jingzhou, Hubei, China Recruiting
• Taihe Hospital
  Shiyan, Hubei, China Recruiting
• The Central Hospital of Wuhan
  Wuhan, Hubei, China Recruiting
• Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technolog
  Wuhan, Hubei, China Recruiting
• Renmin Hospital of Wuhan University
  Wuhan, Hubei, China Recruiting

Study contacts

• Study coordinator: Zhiquan Hu, M.D.
• Email: huzhiquan2000@163.com
• Phone: 86+13971656164

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.