Primary, to show that a single intravesical instillation of chemotherapy immediately before radical surgery for an upper urinary tract (UUT) urothelial carcinoma leads to a 40% reduction in the risk of a subsequent bladder recurrence (urothelial…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
- Ureteric disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary end point is the bladder recurrence rate (histologically proven
urothelial carcinoma) at two years after surgery for an UUT urothelial
carcinoma.
Secondary outcome
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.
Background summary
Following radical nephro-ureterectomy for an upper urinary tract (UUT)
urothelial carcinoma, the reported recurrence rate of a urothelial carcinoma in
the bladder is 22-47%. A meta-analysis showed that a single intravesical
instillation of chemotherapy <10 days after nephro-ureterectomy decreased the
risk of a bladder recurrence by 52%; the absolute risk reduction was 13%; no
serious adverse events were observed. Despite level I evidence, a recent Dutch
survey showed that <10% of treating physicians actually administers an
intravesical instillation of chemotherapy following nephro-ureterectomy. This
reluctance is due to the fact that a fresh wound is present in the bladder
after nephro-ureterectomy, so there is a potential risk of extravasation of
chemotherapy. Extravasation of chemotherapy outside the bladder can lead to
life-threatening complications for the patient. Therefore, we propose a study
of administering a single intravesical instillation of chemotherapy immediately
(<3 hours) before surgery. This will circumvent the risk of extravasation of
chemotherapy making this approach clinically more applicable, which will
improve the compliance of treating physicians.
Study objective
Primary, to show that a single intravesical instillation of chemotherapy
immediately before radical surgery for an upper urinary tract (UUT) urothelial
carcinoma leads to a 40% reduction in the risk of a subsequent bladder
recurrence (urothelial carcinoma) up to two years after surgery compared with
historical controls who received no perioperative intravesical instillation.
Secondly, to show a >80% compliance rate and accurate and consistent protocol
performance of treating physicians. Thirdly, to assess the overall,
cancer-specific, and recurrence-free survival, systematic toxicities, the
quality of life, and the costs of an intravesical instillation with Mitomycin
compared with no perioperative instillation.
Study design
Multicenter, prospective cohort study in a clinical setting.
Intervention
A single intravesical instillation of Mitomycin within three hours before
surgery.
Study burden and risks
Participants will receive a single intravesical instillation of Mitomycin
within three hours before surgery. All participants will complete two
questionnaires (EQ5D-5L and EORTC QLQ-C30) at three different time points.
Investigations during follow-up include cystoscopy and CT-urography, which is
in line with the standardized care and will not include additional
investigations.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
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 CTscan 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.
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
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000949-53-NL |
| CCMO | NL60919.078.17 |
| Other | NL6361 (NTR6545) |
| OMON | NL-OMON24959 |