Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)

Bladder Cancer Clinical Trial

— NAUTICAL  

Official title:

Neoadjuvant Chemotherapy in Upper Tract Urothelial Cancer: A Multicentre, Feasibility Pilot Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04574960
• Other study ID #: 20-5149
• Status: Recruiting
• Phase: Phase 3
• Start date: February 8, 2021
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: Emily Hickey
• Phone: (416) 270-5395
• Email: emily.hickey[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 14
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Bladder Cancer
• Bladder Urothelial Carcinoma
• Carcinoma, Transitional Cell

Intervention

Drug:
• Gemcitabine
Gemcitabine 1000 mg/m^2, IV infusion on days 1 and 8 of each 3-week cycle
• Cisplatin
Cisplatin 70 mg/m^2, IV infusion on day 1 of each 3-week cycle
• Carboplatin
Carboplatin AUC 5-6 calculated using the Calvert formula on day 1 of each cycle

Locations

Country	Name	City	State
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	University Health Network	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Bladder Cancer Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		24 months
Primary	Disease-free survival (DFS)	DFS is defined as the time from randomization to development of intravesical recurrence, contralateral upper tract recurrence or distant metastasis	36 months
Primary	Rate of complete pathologic response	Complete pathologic response is defined as pT0 N0	36 months
Secondary	Site-specific enrolment rate		24 months
Secondary	Number of patients approached per site per month		24 months
Secondary	Number of patients randomized per site per month		24 months