Recruiting

Phase 3

NAUTICALNeoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)

Sponsor:

University Health Network, Toronto

Code:

NCT04574960

Conditions

Bladder Cancer

Bladder Urothelial Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Gemcitabine

Cisplatin

Carboplatin

Study Details

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.

Conditions

Bladder Cancer

Bladder Urothelial Carcinoma

Study ID

NCT04574960

Start date

Feb 8, 2021

Status verified date

Jul, 2025

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

14 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Neoadjuvant Chemotherapy Arm

Gemcitabine/Cisplatin will be administered on a 3-week cycle for up to 4 cycles. This will be followed by surgical intervention (nephroureterectomy or ureterectomy).

active comparator: Adjuvant Chemotherapy Arm (Standard of Care)

Patients will undergo surgical intervention (nephroureterectomy or ureterectomy) followed by adjuvant chemotherapy.

Patients with a GFR greater or equal to 60 mL/min will receive Gemcitabine/Cisplatin while those with a GFR greater or equal to 30 mL/min but less than 60 mL/min will receive Gemcitabine/Carboplatin.

Gemcitabine/Cisplatin will be administered on a 3-week cycle for up to 4 cycles.

Gemcitabine/Carboplatin will be administered on a 3-week cycle for up to 4 cycles.

Interventions

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

Primary outcome 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 [ Time Frame: 24 months ]
Disease-free survival (DFS) [ Time Frame: 36 months ]
Rate of complete pathologic response [ Time Frame: 36 months ]

Central Contacts and Locations

Central contacts

Emily Hickey

(416) 270-5395 emily.hickey@uhn.ca

Locations

The Ottawa Hospital

Recruiting

Ottawa, Ontario, Canada, K1H8L6

Contacts

Pascale Juneau

613-737-8899 pjuneau@ohri.ca

Principal Investigator:

Rodney Breau, MD

University Health Network

Recruiting

Toronto, Ontario, Canada, M5G2M9

Contacts

Sarah Cheung

(437) 335-2949 sarah.cheung@uhn.ca

Principal Investigator:

Girish Kulkarni, MD

More Information

Sponsor

University Health Network, Toronto

Last update posted

Jul 20, 2025

Last verified

Jul, 2025

Keywords

Upper tract urothelial carcinoma
UTUC

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University Health Network, Toronto on 2025-07-20.