Clinical trial NCT04574960: Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)
Official title: Neoadjuvant Chemotherapy in Upper Tract Urothelial Cancer: A Multicentre, Feasibility Pilot Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Bladder Cancer
Bladder Urothelial Carcinoma
Keywords: Upper tract urothelial carcinoma
UTUC
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Bladder Cancer Canada
First posted: 2020-10-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Upper tract urothelial cancer (UTUC) is cancer in the lining of the kidney or ureter (the tube that drains the kidney). This type of cancer is rare and as a result, there are only a few studies that have looked at it.

Standard of care for UTUC would be surgery followed by chemotherapy (adjuvant chemotherapy). However, we know from studies that have looked at cancer of the lining of the bladder, which is a similar cancer in many ways, that treating people with chemotherapy before surgery (neoadjuvant chemotherapy) can lead to longer survival compared to the standard of care. There are no studies to show this in UTUC. Neoadjuvant chemotherapy is thought to help improve survival by treating any cancer that may have spread from the original tumour but that is not visible yet on scans. This study would be the first clinical trial in Canada to evaluate the use of chemotherapy before surgery in this disease setting.

Since UTUC is rare, the purpose of this study is to determine if it is possible to enrol enough patients to a trial looking at the use of chemotherapy before surgery.


Eligibility criteria: Inclusion Criteria:

* Newly diagnosed radiographically visible (CT or MRI) cT1-4 N0 M0 with positive selective urinary cytology, positive bladder urinary cytology, or endoscopic biopsy for high grade urothelial cell carcinoma
* Age ≥18 years of age
* Eastern Cooperative Oncology Group (ECOG) score 0-1
* Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per participating site attending urologic oncologist
* Medically appropriate candidate for cisplatin-based chemotherapy as per participating site attending medical oncologist
* Adequate organ system function defined as follows: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,00/mm3, hemoglobin ≥ 90 g/L, ALT and AST \< 2.5 x upper limit of normal, electrolytes (Na, K, Mg, Ca): within normal limits, GFR ≥ 60 mL/min

Patients who are randomized to the adjuvant chemotherapy will be reassessed for suitability to receive adjuvant chemotherapy after definitive surgery (nephroureterectomy or ureterectomy) based on the following criteria:

* pT2-4 N0-3 M0 or pT any N1-3 M0 with predominant urothelial component
* ECOG score 0-2
* Medically appropriate candidate for platin-based chemotherapy as per participating site attending medical oncologist
* Adequate organ system function defined as follows: absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,00/mm3, hemoglobin ≥ 90 g/L, ALT and AST \< 2.5 x upper limit of normal, electrolytes (Na, K, Mg, Ca): within normal limits, GFR ≥ 30 mL/min

Exclusion Criteria:

* Metastatic disease
* Radiographically visible nodal disease
* Concurrent muscle-invasive bladder cancer (non-muscle invasive bladder cancer is acceptable)
* Solitary kidney
* Other cancer diagnosis or systemic chemotherapy use within 2 years of study enrollment (prior bladder cancer and intravesical therapy allowed)
* Concomitant diseases that are a formal exclusion to cisplatin chemotherapy (deafness, ≥ grade II neuropathy, serious active infection)
* Concomitant use of any other investigational drugs
* Pregnancy or breast feeding (you must remain on contraception, not father a child or donate sperm while receiving gemcitabine/cisplatin and for 6 months following the last dose)

Primary outcomes:
measure: Feasibility of enrolling cT1-4N0 M0 UTUC patients in a randomized trial of neoadjuvant chemotherapy versus standard of care by assessing pilot trial recruitment rates
timeFrame: 24 months
measure: Disease-free survival (DFS)
timeFrame: 36 months
measure: Rate of complete pathologic response
timeFrame: 36 months
Secondary outcomes:
measure: Site-specific enrolment rate
timeFrame: 24 months
measure: Number of patients approached per site per month
timeFrame: 24 months
measure: Number of patients randomized per site per month
timeFrame: 24 months
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network - Princess Margaret Hospital
name: Girish Kulkarni, MD
role: PRINCIPAL_INVESTIGATOR
References: