Bladder CancerPhase 3NAUTICALNCT04574960
Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)
A Phase 3 study testing Gemcitabine, Cisplatin and Carboplatin in people with Bladder Cancer and Bladder Urothelial Carcinoma, run by University Health Network, Toronto at 2 sites in Canada.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Bladder Urothelial Carcinoma
- What is being tested?
- Gemcitabine, Cisplatin and Carboplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesCanada
- Study dates
- 8 Feb 2021to Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Recruiting
The Ottawa Hospital
Ottawa, Ontario, K1H8L6
Pascale Juneau, 613-737-8899 ext. 73852, pjuneau@ohri.ca
Rodney Breau, MD
- Recruiting
University Health Network
Toronto, Ontario, M5G2M9
Sarah Cheung, (437) 335-2949, sarah.cheung@uhn.ca
Girish Kulkarni, MD
About this study
Official title: Neoadjuvant Chemotherapy in Upper Tract Urothelial Cancer: A Multicentre, Feasibility Pilot Trial
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
- Being tested
- Gemcitabine, Cisplatin, Carboplatin
- Keywords
- Upper tract urothelial carcinoma, UTUC
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called Gemzar
Gemcitabine 1000 mg/m^2, IV infusion on days 1 and 8 of each 3-week cycle
CisplatinDrug
Also called Platinol
Cisplatin 70 mg/m^2, IV infusion on day 1 of each 3-week cycle
CarboplatinDrug
Also called Paraplatin
Carboplatin AUC 5-6 calculated using the Calvert formula on day 1 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Chemotherapy Arm | Experimental | 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). Receives: Drug: Gemcitabine; Drug: Cisplatin |
| Adjuvant Chemotherapy Arm (Standard of Care) | Active comparator | 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. Receives: Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24 months
Disease-free survival (DFS)
DFS is defined as the time from randomization to development of intravesical recurrence, contralateral upper tract recurrence or distant metastasis
Measured: 36 months
Rate of complete pathologic response
Complete pathologic response is defined as pT0 N0
Measured: 36 months
Secondary outcomes (3)
Site-specific enrolment rate
Measured: 24 months
Number of patients approached per site per month
Measured: 24 months
Number of patients randomized per site per month
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start8 Feb 2021
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Bladder Cancer Canada
- Responsible party
- Sponsor
- Investigators
- Girish Kulkarni, MD, Principal investigator, University Health Network - Princess Margaret Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04574960
- Sponsor's protocol ID
- 20-5149
- Acronym
- NAUTICAL
- Status last verified
- Oct 2026
- First submitted
- 18 Sep 2020
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Chemotherapy in Upper Tract Urothelial Cancer: A Multicentre, Feasibility Pilot Trial
- ClinicalTrials.gov ID
- NCT04574960
- Acronym / sponsor ID
- NAUTICAL / 20-5149
- Conditions
- Bladder Cancer, Bladder Urothelial Carcinoma
- Keywords
- Upper tract urothelial carcinoma, UTUC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Bladder Cancer Canada
- Study start
- 8 Feb 2021 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 5 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Chemotherapy Arm | Experimental | Drug: Gemcitabine, Drug: CisplatinGemcitabine/Cisplatin will be administered on a 3-week cycle for up to 4 cycles. This will be followed by surgical intervention (nephroureterectomy or ureterectomy). |
| Adjuvant Chemotherapy Arm (Standard of Care) | Active comparator | Drug: Gemcitabine, Drug: Cisplatin, Drug: CarboplatinPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GemcitabineAlso: GemzarGemcitabine 1000 mg/m^2, IV infusion on days 1 and 8 of each 3-week cycle | Drug | Adjuvant Chemotherapy Arm (Standard of Care), Neoadjuvant Chemotherapy Arm |
| CisplatinAlso: PlatinolCisplatin 70 mg/m^2, IV infusion on day 1 of each 3-week cycle | Drug | Adjuvant Chemotherapy Arm (Standard of Care), Neoadjuvant Chemotherapy Arm |
| CarboplatinAlso: ParaplatinCarboplatin AUC 5-6 calculated using the Calvert formula on day 1 of each cycle | Drug | Adjuvant Chemotherapy Arm (Standard of Care) |
Primary outcome
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
DFS is defined as the time from randomization to development of intravesical recurrence, contralateral upper tract recurrence or distant metastasis
Rate of complete pathologic response
Time frame: 36 months
Complete pathologic response is defined as pT0 N0
3 secondary outcomes
Site-specific enrolment rate
Time frame: 24 months
Number of patients approached per site per month
Time frame: 24 months
Number of patients randomized per site per month
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Girish Kulkarni, MD principal investigator
University Health Network - Princess Margaret Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gemcitabine, Cisplatin and Carboplatin in people with Bladder Cancer and Bladder Urothelial Carcinoma, run by University Health Network, Toronto at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Emily Hickey ((416) 270-5395, emily.hickey@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.