Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)

NCT04574960 | Recruiting Phase 3 DMC

• 1 other identifier: 20-5149
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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

Keywords

Upper tract urothelial carcinoma; UTUC

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• Rate of complete pathologic response

  Complete pathologic response is defined as pT0 N0

  36 months

Secondary Outcomes (3)

• Site-specific enrolment rate

  24 months

• Number of patients approached per site per month

  24 months

• Number of patients randomized per site per month

  24 months

Study Arms (2)

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).

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.

Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

Interventions

Gemcitabine DRUG

Gemcitabine 1000 mg/m\^2, IV infusion on days 1 and 8 of each 3-week cycle

Also known as: Gemzar

Adjuvant Chemotherapy Arm (Standard of Care); Neoadjuvant Chemotherapy Arm

Cisplatin DRUG

Cisplatin 70 mg/m\^2, IV infusion on day 1 of each 3-week cycle

Also known as: Platinol

Adjuvant Chemotherapy Arm (Standard of Care); Neoadjuvant Chemotherapy Arm

Carboplatin DRUG

Carboplatin AUC 5-6 calculated using the Calvert formula on day 1 of each cycle

Also known as: Paraplatin

Adjuvant Chemotherapy Arm (Standard of Care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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)

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Bladder Cancer Canada: collaborator

Study Sites (2)

The Ottawa Hospital

Ottawa, Ontario, K1H8L6, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G2M9, Canada

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Gemcitabine; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Girish Kulkarni, MD

  University Health Network - Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily Hickey

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: October 5, 2020
• Study Start: February 8, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 20, 2025

Record last verified: 2025-07

Locations

CA (2)