Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)

NCT ID: NCT04574960

Last Updated: 2025-07-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-08
• Study Completion Date: 2027-12-31

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 Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Interventions

Gemcitabine

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Other Intervention Names

Gemzar; Platinol; Paraplatin

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bladder Cancer Canada

UNKNOWN

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Girish Kulkarni, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network - Princess Margaret Hospital

Locations

The Ottawa Hospital

Ottawa, Ontario, Canada

Site Status: RECRUITING

University Health Network

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Emily Hickey

Role: CONTACT

emily.hickey@uhn.ca

(416) 270-5395

Facility Contacts

Pascale Juneau

Role: primary

pjuneau@ohri.ca

613-737-8899 ext. 73852

Sarah Cheung

Role: primary

sarah.cheung@uhn.ca

(437) 335-2949

Other Identifiers

20-5149

Identifier Type: -

Identifier Source: org_study_id