Upper Tract Urothelial Carcinoma (UTUC). MedDRA version: 20.0 Level: HLGT Classification code 10038364 Term: Renal and urinary tract neoplasms malignant and unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLGT Classification code 10038365 Term: Renal and urinary tract therapeutic procedures System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Name: Mitomycin
Pharmaceutical Form: Powder for intravesical solution
INN or Proposed INN: MITOMYCIN
CAS Number: 50-07-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentra
Sponsors
Erasmus MC, Dept. Urology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with histologically proven urothelial carcinoma of the UUT with or without concurrent carcinoma in situ (CIS only is also allowed) or patients with a suspicion of a urothelial carcinoma of the UUT on CT-scan with or without a urinary cytology sample suspicious of the presence of high-grade urothelial carcinoma. In case urinary cytology shows no abnormality and no diagnostic URS is done, conclusive results of the CT-urography are sufficient for inclusion and the coordinating investigator will evaluate the eligibility of the subject in consultation with the local investigator. - Patients treated either by partial ureterectomy or by a radical nephro-ureterectomy (open or laparoscopic) including a bladder cuff. - Age = 18 years. - WHO performance status 0,1, or 2. - Negative pregnancy test in women with childbearing potential. - Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: - If pre-operative histology obtained by biopsy: aberrant histology of the UUT tumor of >50% (adenocarcinoma, small cell carcinoma, squamous cell carcinoma). - Postoperative pathological report shows absence of tumor (pT0) or >50% of the UUT tumor shows aberrant histology . - History or presence of a malignant tumor or carcinoma in situ of the bladder. - History of UUT urothelial carcinoma on the contralateral side or presence of bilateral UUT urothelial carcinoma. - Known allergy against Mitomycin. - Anticipated adjuvant intravesical treatment with chemo- or immunotherapy. - Anticipated adjuvant intravesical treatment with chemo- or immunotherapy following a diagnostic URS. - Acute urinary tract infection at the time of inclusion as assessed by urinary culturing. - Lymphadenopathy or distant metastases as assessed by preoperative CT-scan of thorax and abdomen. - Any other concurrent severe or uncontrolled disease preventing the safe administration of intravesical Mitomycin. - Breastfeeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show that a single intravesical instillation of chemotherapy immediately (<2 hours) before radical nephro-ureterectomy or partial ureterectomy for a urothelial carcinoma of the UUT reduces the risk of a subsequent urothelial bladder cancer recurrence up to two years after surgery with 40% compared with a matched historical cohort who received no perioperative intravesical instillations.;Secondary Objective: To show a =80% compliance rate and accurate and consistent protocol performance of a single neoadjuvant instillation with Mitomycin three hours before radical nephro-ureterectomy or partial ureterectomy for a urothelial carcinoma of the UUT. In addition, to assess the 2-year overall, cancer-specific, and recurrence-free survival, the quality of life, and the costs of a single neoadjuvant instillation with Mitomycin before radical nephro-ureterectomy or partial ureterectomy for an UUT urothelial carcinoma compared with no perioperative intravesical instillations. Lastly, a genomic characterization of UUT urothelial carcinoma and subsequent bladder cancer recurrences within the same patients by whole genome sequencing.;Primary end point(s): The primary end point is the bladder recurrence rate (histologically proven urothelial carcinoma) at two years after surgery for an UUT urothelial carcinoma. ;Timepoint(s) of evaluation of this end point: Two years after surgery. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To show a >80% compliance rate and accurate and consistent protocol performance of treating physicians. 2) The overall, cancer-specific, and recurrence-free survival at two years after surgery. 3) The toxicity of the regimen at three months (CTCAE version 4.0). 4) The quality of life of the subjects will be assessed at inclusion (T0, before surgery and neo-adjuvant treatment), at two weeks (T2) and three months (T3) after surgery. The EQ5D-5L and the EORTC QLQ-C30 will be used. 5) Costs from a societal perspective using a time horizon of two years. The costs consist of direct costs (e.g., personnel costs of health professionals involved, disorder related medication, disorder related innervations, time duration of hospital, informal care) and indirect costs (productivity loss) associated with each regimen. 6) Incremental cost-effectiveness ratios. The economic evaluation will be a cost-utility analysis and a cost-effectiveness analysis performed from a societal perspective. 7) At inclusion, patients will be asked to provide consent on the use of their tumor tissue for molecular analysis. Whole genome sequencing will be performed to investigate tumor-specific somatic mutations and copy number variations to compare the molecular profile of the primary UUT tumor and subsequent bladder tumor.;Timepoint(s) of evaluation of this end point: T0 (before surgery and neo-adjuvant treatment), at two weeks (T2) and three months (T3) after surgery. | — |
Countries
Netherlands
Contacts
Public ContactCoordinating Investigator
Erasmus MC
Outcome results
None listed