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

Primary Purpose

Bladder Cancer, Bladder Urothelial Carcinoma

Status

Recruiting

Phase

Phase 3

Locations

Canada

Study Type

Interventional

Intervention

Gemcitabine

Cisplatin

Carboplatin

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring Upper tract urothelial carcinoma, UTUC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Newly diagnosed radiographically visible (CT or MRI) cT1-4 N0 M0 with positive selective 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)

Sites / Locations

University Health NetworkRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Neoadjuvant Chemotherapy Arm

Adjuvant Chemotherapy Arm (Standard of Care)

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

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

Disease-free survival (DFS)

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

Complete pathologic response is defined as pT0 N0

Secondary Outcome Measures

Site-specific enrolment rate

Number of patients approached per site per month

Number of patients randomized per site per month

Full Information

NCT ID

NCT04574960

First Posted

September 18, 2020

Last Updated

July 28, 2023

Sponsor

University Health Network, Toronto

Collaborators

Bladder Cancer Canada

1. Study Identification

Unique Protocol Identification Number

NCT04574960

Brief Title

Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)

Acronym

NAUTICAL

Official Title

Neoadjuvant Chemotherapy in Upper Tract Urothelial Cancer: A Multicentre, Feasibility Pilot Trial

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 8, 2021 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

February 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

Collaborators

Bladder Cancer Canada

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bladder Cancer, Bladder Urothelial Carcinoma

Keywords

Upper tract urothelial carcinoma, UTUC

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

14 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Neoadjuvant Chemotherapy Arm

Arm Type

Experimental

Arm Description

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).

Arm Title

Adjuvant Chemotherapy Arm (Standard of Care)

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemzar

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

Platinol

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Paraplatin

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Title

Disease-free survival (DFS)

Description

DFS is defined as the time from randomization to development of intravesical recurrence, contralateral upper tract recurrence or distant metastasis

Time Frame

36 months

Title

Rate of complete pathologic response

Description

Complete pathologic response is defined as pT0 N0

Time Frame

36 months

Secondary Outcome Measure Information:

Title

Site-specific enrolment rate

Time Frame

24 months

Title

Number of patients approached per site per month

Time Frame

24 months

Title

Number of patients randomized per site per month

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Emily Hickey

Phone

(416) 270-5395

emily.hickey@uhn.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Girish Kulkarni, MD

Organizational Affiliation

University Health Network - Princess Margaret Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Health Network

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G2M9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sarah Cheung

Phone

(437) 335-2949

sarah.cheung@uhn.ca

First Name & Middle Initial & Last Name & Degree

Girish Kulkarni, MD

12. IPD Sharing Statement

Learn more about this trial

Neoadjuvant Upper Tract Invasive Cancer Trial (NAUTICAL)

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