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

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ClinicalTrials.gov Identifier: NCT04574960
Recruitment Status : Recruiting
First Posted : October 5, 2020
Last Update Posted : April 13, 2022
Sponsor:
Collaborator:
Bladder Cancer Canada
Information provided by (Responsible Party):
University Health Network, Toronto

Study Description
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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.


Condition or disease Intervention/treatment Phase
Bladder Cancer Bladder Urothelial Carcinoma Drug: Gemcitabine Drug: Cisplatin Drug: Carboplatin Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Chemotherapy in Upper Tract Urothelial Cancer: A Multicentre, Feasibility Pilot Trial
Actual Study Start Date : February 8, 2021
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: Gemzar

Drug: Cisplatin
Cisplatin 70 mg/m^2, IV infusion on day 1 of each 3-week cycle
Other Name: 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 Name: Gemzar

Drug: Cisplatin
Cisplatin 70 mg/m^2, IV infusion on day 1 of each 3-week cycle
Other Name: Platinol

Drug: Carboplatin
Carboplatin AUC 5-6 calculated using the Calvert formula on day 1 of each cycle
Other Name: Paraplatin


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
  2. 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

  3. Rate of complete pathologic response [ Time Frame: 36 months ]
    Complete pathologic response is defined as pT0 N0


Secondary Outcome Measures :
  1. Site-specific enrolment rate [ Time Frame: 24 months ]
  2. Number of patients approached per site per month [ Time Frame: 24 months ]
  3. Number of patients randomized per site per month [ Time Frame: 24 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04574960


Contacts
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Contact: Lena Sundaram (416) 634-8219 lena.sundaram2@uhn.ca

Locations
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Canada, Ontario
University Health Network Recruiting
Toronto, Ontario, Canada, M5G2M9
Contact: Sarah Cheung    (437) 335-2949    sarah.cheung@uhn.ca   
Principal Investigator: Girish Kulkarni, MD         
Sponsors and Collaborators
University Health Network, Toronto
Bladder Cancer Canada
Investigators
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Principal Investigator: Girish Kulkarni, MD University Health Network - Princess Margaret Hospital
More Information
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04574960    
Other Study ID Numbers: 20-5149
First Posted: October 5, 2020    Key Record Dates
Last Update Posted: April 13, 2022
Last Verified: April 2022

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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
Keywords provided by University Health Network, Toronto:
Upper tract urothelial carcinoma
UTUC
Additional relevant MeSH terms:
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Carcinoma, Transitional Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Carboplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
 Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs