Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL) (NAUTICAL)

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.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer; Bladder Urothelial Carcinoma
• Intervention / Treatment: Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Emily Hickey; Phone Number: (416) 270-5395; Email: emily.hickey@uhn.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • Recruiting
      • The Ottawa Hospital
      • Contact: Pascale Juneau; Phone Number: 73852 613-737-8899; Email: pjuneau@ohri.ca
      • Principal Investigator: Rodney Breau, MD
    • Toronto, Ontario, Canada, M5G2M9
      • Recruiting
      • University Health Network
      • Contact: Sarah Cheung; Phone Number: (437) 335-2949; Email: sarah.cheung@uhn.ca
      • Principal Investigator: Girish Kulkarni, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Drug: Gemcitabine; Gemcitabine 1000 mg/m^2, IV infusion on days 1 and 8 of each 3-week cycle; Other Names: Gemzar; Drug: Cisplatin; Cisplatin 70 mg/m^2, IV infusion on day 1 of each 3-week cycle; Other Names: Platinol
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.	Drug: Gemcitabine; Gemcitabine 1000 mg/m^2, IV infusion on days 1 and 8 of each 3-week cycle; Other Names: Gemzar; Drug: Cisplatin; Cisplatin 70 mg/m^2, IV infusion on day 1 of each 3-week cycle; Other Names: Platinol; Drug: Carboplatin; Carboplatin AUC 5-6 calculated using the Calvert formula on day 1 of each cycle; Other Names: Paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Bladder Cancer Canada
• Investigators: Principal Investigator: Girish Kulkarni, MD, University Health Network - Princess Margaret Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 18, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: UTUC; Upper tract urothelial carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma, Transitional Cell; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Carboplatin; Gemcitabine
• Other Study ID Numbers: 20-5149

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No