Upper Urinary Tract Urothelial Carcinoma

This study will evaluate the efficacy and safety of UGN-104, a new formulation of UGN-101 (approved in the United States and Israel as JELMYTO \[mitomycin\] for pyelocalyceal solution), instilled in the upper urinary tract (UUT) of patients with low-grade upper tract urothelial cancer (LG-UTUC).

This is a prospective, single-center, single-arm phase II study evaluating whether a single postoperative intravesical instillation of disitamab vedotin (RC48) can reduce bladder recurrence after radical nephroureterectomy (RNU) in patients with HER2-positive upper tract urothelial carcinoma (UTUC). Eligible patients will receive one intravesical instillation of RC48 within 96 hours after surgery. The primary objective is to determine the 12-month intravesical recurrence rate. Serial urine samples will be prospectively collected to evaluate urinary methylation biomarkers for early recurrence detection.

This is a study looking at how patients with a rare type of cancer in the pelvis and ureter of the kidney - called upper urinary tract urothelial carcinoma (UTUC) - is currently treated. The gold standard treatment of UTUC is the complete removal of the kidney, renal pelvis and ureter. The use of kidney-sparing surgery, which preserves the kidney while treating the cancer, was only considered for patients who were too frail to undergo kidney removal, had a solitary functioning kidney, or suffered from severe chronic kidney disease. Since 2018 international guidelines have incorporated kidney sparing surgery for all patients but only offered to patients that have been diagnosed with very low risk tumors to ensure the safety of the patients. The latest update of the UTUC Guidelines from the European Association of Urology has revised the criteria, so that certain features previously classified as high-risk are no longer considered high-risk on their own, provided the tumor otherwise appears benign. Nonetheless, ongoing research is essential to support this evolving approach and to further enhance the guidelines. Kidney sparing surgery comprise of a strict follow up schedule that often demands supplemental surgeries under general anesthesia, which can cause strain on patients. Preservation of the kidney is important since a decrease in kidney function can result in increased risk of cardiovascular disease and death. The main question we want to answer is: Can more patients with superficial non-invasive UTUC safely be treated with kidney-sparing surgery instead of the more aggressive surgery that removes the entire kidney and ureter without increasing the risk of the cancer coming back and while maintaining quality of life? Furthermore, we are interested in learning more about patients who later develop bladder cancer after treatment of UTUC (intravesical recurrences), the affection of kidney function over time and a subgroup of UTUC patients that are diagnosed with Lynch syndrome (a genetic condition that increases cancer risk and development of UTUC is the third most common cancer) where UTUC presents differently than other patients. Participants Anyone diagnosed with UTUC can take part in the study. We will collect information from their medical records when they join and again after one, three, five, and ten years. Participants will also be asked to fill out quality-of-life questionnaires at the beginning of entering the study and at one, three and five years.

In this study, 60 patients with HER2 overexpression UTUC with high-risk recurrence factors after radical surgery were proposed to be enrolled, and were assigned to Cohort I (receiving adjuvant therapy group) and Cohort II (refusing to receive adjuvant therapy group) according to the subjects' wishes. Cohort I subjects were treated with vedicloxacinumab in combination with radiotherapy, and vedicloxacinumab treatment lasted for 6 months. Cohort II subjects receive close observation and best supportive care. Safety evaluations and efficacy evaluations will be performed during the study period. Safety Evaluations: Safety evaluations will be conducted within 3 days prior to each dose and will continue until 30 days after the last study dose or initiation of new antitumor therapy for subjects who have received at least one dose of study drug. Evaluation of effectiveness: effectiveness evaluations will be conducted every 12 weeks (±3 days) until imaging-confirmed tumor recurrence, subject death, withdrawal of informed consent, loss to follow-up, or study termination, whichever occurs first. Tumor assessment was performed according to the Criteria for Evaluation of Efficacy in Solid Tumors (RECIST v1.1). For subjects with disease progression, postoperative tumor recurrence, or initiation of other antitumor therapy, survival follow-up was performed every 3 months (window period ± 14 days) from the date of notification to collect information on the subject's subsequent antitumor therapy and survival until the subject's death, withdrawal of informed consent, loss of visit, or study termination, whichever occurred first.

This is a prospective, open, multiple-center clinical study of renal preservation therapy in high-risk upper urinary tract urothelial carcinoma patients . The study was conducted in accordance with the Good Practice for Quality Control of Clinical Trials for Pharmaceutical Products (GCP). Approximately 20 subjects will be enrolled to evaluate the efficacy and safety of RC48 (2.0 mg/kg intravenously every 3 weeks) combined with Tislelizumab (200mg intravenously every 3 weeks).

Approximately 20 participants will be enrolled in the study to evaluate the efficacy and safety of the combination of DV (DV, 2.0 mg/kg, intravenously administered every 2 weeks) and toripalimab (toripalimab, 3.0mg/kg, intravenously administered every 2 weeks). Subjects will receive 6 cycles of DV and toripalimab, followed by laser surgery to remove ureteral or renal pelvis tumors, followed by 12 cycles of DV and 1 year of toripalimab consolidation therapy. Efficacy and safety were evaluated by cystoscopy, ureteroscopy, laboratory tests, and imaging examinations after treatment.

Observational study on relapse occurrence and on the quality of life in patients who underwent nephroureterectomy surgery

Study design This study is a Phase III, randomized, open-label, multi-center, global study to determine the efficacy of a single immediate intravesical chemotherapy instillation (SI) in the prophylaxis of intravesical recurrence after diagnostic uretero-renoscopy (URS) of patients 18 years of age or older with the fist diagnosis of UTUC. This study will randomize 394 patients globally Patients will be randomized in a 1:1 ratio to the interventional arm or to observation. Study period This study will include a screening period, a treatment and disease assessment period, safety follow-up visits and a 5-year survival follow-up period to begin immediately after the treatment. Screening period: The period up to 28 days prior to intervention during which the screening procedures occur. Treatment and disease assessment period: The period starting the day of diagnostic URS (Day 0) during which patients receive their assigned treatment (Day 0 to day 1) and disease assessments are performed. All patients must follow the disease assessment schedule, which includes disease assessments at screening and every 3 months (±1 week) from the date of intervention until 24 months from the date of randomization, and then every 6 months for up to 5 years. The treatment and disease assessment period will end at the time of intravesical recurrence, death, or MINERVA-CTU decision to terminate the trial early. Safety follow-up visits: Every patient in this study will be assessed for the occurrence of adverse events (AEs) and serious adverse events from the time of signed informed consent until 90 days after the administration of SI. All patients who receive SI will have safety visits 4, 8, and 12 weeks following administration of SI. Safety assessments include targeted physical examination, complications according to Dindo-Clavien classification and patient-reported outcomes (PRO) assessments. Survival follow-up period: Patients will be followed up at in-clinic site visits, by telephone contact, or by contact with the patient's current physician for up to 5 years from the date of randomized into this study. Objectives Primary objective Efficacy of a SI in the prophylaxis of intravesical recurrence after diagnostic URS for UTUC Secondary objectives * Time to intravesical recurrence * 5-years intravesical recurrence rates * Incidence of high-grade BCa recurrence * Incidence and gravity of adverse events (AEs) due to the SI * To collect and store blood, urine and tissue samples according to each country's local and ethical procedures for identifying candidate markers that may correlate with likelihood of clinical benefit (optional) * To collect and store DNA according to each country's local and ethical procedures for future exploratory research into somatic mutations and genes/genetic variations that may influence oncologic outcomes, to study treatments and susceptibility to disease (optional) * To assess disease-related symptoms and HRQoL in patients with UTUC treated with SI compared those undergoing observation * To assess patient-reported treatment tolerability directly using specific PRO-CTCAE symptoms Target study population The study population includes patients 18 years of age or older with a primary diagnosis of UTUC, scheduled for diagnostic URS Duration of treatment Patients randomized to the interventional arm will receive a SI within 24h after diagnostic URS. In case of multiple diagnostic URS during the follow-up (including 2nd look for incomplete ablation, non-diagnostic first URS or UTUC recurrence) patients randomized to the interventional arm will receive a SI after each diagnostic URS for 2 years after the day of first diagnostic URS. Follow-up of subjects post discontinuation of study treatment Patients who have discontinued study treatment due to toxicity, symptomatic deterioration, intravesical recurrence or investigator's decision will be followed up for survival until 5 years from the date of diagnostic URS. Survival All randomized patients, regardless of disease status, will be followed up for survival until 5 years from the date of diagnostic URS. Investigational product, dosage, and mode of administration Patients randomized to the interventional arm will receive a SI. The chemotherapy will be at investigator's discretion and institutional availability. The selected chemotherapy must be approved by the MINERVA-CTU in discussion with the local investigator. Statistical methods This study will randomize 394 patients globally. Patients will be randomized 1:1 to SI or observation. Randomization will be stratified by the following factors: 1. Center 2. EAU UTUC risk stratification