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Feasibility of Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma (URANUS)

Primary Purpose

Upper Tract Urothelial Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RNU
Gemcitabine/Cisplatin
M-VAC Protocol
Sponsored by
The European Uro-Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Upper Tract Urothelial Carcinoma focused on measuring UTUC, Upper Tract Urothelial Carcinoma, Neoadjuvant chemotherapy, Adjuvant chemotherapy, Radical nephroureterectomy

Eligibility Criteria

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

Inclusion Criteria:

  • Written informed consent
  • Age > 18 years
  • Histological and radiological defined UTUC: Histologically-confirmed diagnosis of predominantly urothelial carcinoma of the upper urinary tract Patients with UTUC cT2-pT4 cN0-N1 M0 (TNM classification)
  • Women with negative serum pregnancy test within 14 days of first dose of study treatment and agreement to use effective contraception
  • Patients without bladder cancer or with concomitant non muscle invasive bladder cancer
  • Adequate organ system function defined as follows: Hematologic: Absolute neutrophil count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L (9.02g/dL); Platelets 100 X 109/L; Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated partial thromboplastin time (aPTT)1.2 X Upper limit of normal (ULN). Hepatic: Total bilirubin 1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) 2.5 X ULN. Renal: GRF <or> 55 ml/min: Electrolytes: potassium and calcium: within normal limits.
  • CT scan of the chest, abdomen and pelvis and Bone scan without evidence of distant metastasis

Exclusion Criteria:

  • Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
  • History of cardiovascular conditions within the past 6 months.
  • Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an exclusion criteria but requires anticoagulation treatment.
  • Any major contraindication to a surgical procedure.
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Active infection contraindicating chemotherapy
  • Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin cancer or prostate cancer T1 Gleason <7, Prostate specific antigen (PSA) <10. Patients with past medical history of cancer can be included if diagnosed at least 4 years ago.
  • Concomitant muscle invasive bladder cancer
  • Patients who have been or still are on methotrexate treatment.

Sites / Locations

  • Radboud University Medical CentreRecruiting
  • Leiden University Medical CentreRecruiting
  • Alrijne ZiekenhuisRecruiting
  • Canisius Wilhelmina ZiekenhuisRecruiting
  • Haukeland University HospitalRecruiting
  • Complejo Hospitalario Universitario A Coruña
  • Hospital Universitario German Trias i PujolRecruiting
  • Fundacion PuigvertRecruiting
  • Hospital Clinico de Barcelona
  • Hospital San PauRecruiting
  • Hospital Universitario Vall d'Hebron
  • Hospital Universitario de Basurto
  • Hospital Universitari de Girona Doctor Josep TruetaRecruiting
  • Hospital Universitario Clínico San CecilioRecruiting
  • Hospital de Jerez
  • Hospital Complex Insular-Materno Infantil
  • Clinica Universitaria de NavarraRecruiting
  • Fundacion Jimenez Diaz
  • Hospital ramón y CajalRecruiting
  • Hospital Universitario La PazRecruiting
  • Hospital Clinico Universitario Virgen de la ArrixacaRecruiting
  • Hospital General Universitario Morales Meseguer
  • Complejo Hospitalario de NavarraRecruiting
  • Hospital Parc TaulíRecruiting
  • Hospital Universitario de SalamancaRecruiting
  • Hospital Universitario Marques de ValdecillaRecruiting
  • Hospital Virgen del RocioRecruiting
  • Fundacion Instituto Valenciano de Oncologia
  • Hospital Clinico Universitario Lozano Blesa

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Other

Other

Other

Other

Other

Arm Label

Radical nephro-ureterectomy (RNU)

Gemcitabine/Cisplatin plus RNU

RNU plus Gemcitabine/Cisplatin

M-VAC protocol plus RNU

RNU plus M-VAC protocol

Arm Description

Patients who dont fulfil inclusion criteria for chemotherapy treatment randomization (poor renal function: Glomerular Filtration Rate (GFR) <55 ml/min or unfit for cisplatin-based chemotherapy)

Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks before surgery

Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks after surgery

Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) before surgery

Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) after surgery

Outcomes

Primary Outcome Measures

Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
Percentage of patients randomised to adjuvant or neo-adjuvant treatment

Secondary Outcome Measures

Disease Free Survival (DFS)
time from randomisation to local recurrence or distant metastasis
Overall Survival (OS)
time from randomisation to death for any cause different from urothelial carcinoma
Cancer-Specific Survival (CSS)
time from randomisation to death from urothelial carcinoma

Full Information

First Posted
November 11, 2016
Last Updated
March 7, 2023
Sponsor
The European Uro-Oncology Group
Collaborators
Centre for Human Drug Research, Netherlands
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1. Study Identification

Unique Protocol Identification Number
NCT02969083
Brief Title
Feasibility of Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma
Acronym
URANUS
Official Title
Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 28, 2018 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The European Uro-Oncology Group
Collaborators
Centre for Human Drug Research, Netherlands

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of this study is to explore feasibility of Upper Tract Urothelial Carcinoma (UTUC) treatments based in real world data in various European countries. The study will allow to gain insight in the true proportion of patients that fit to receive complete cisplatin-based neo-adjuvant or adjuvant chemotherapy, and the proportion and clinical outcome of patients with poor prognostic factors (PS and renal function) who receive only standard treatment (Radical nephroureterectomy (RNU)). This comparison will be made using a uniform diagnostic and treatment protocol.
Detailed Description
There are no definitive treatment recommendations for patients diagnosed with UTUC. Radical nephroureterectomy (RNU) has been considered the gold standard treatment for UTUC. However due to the high recurrence rates reported, patients are often offered perioperative chemotherapy provided that they have a good renal function and performance status. With regard to the choice of chemotherapy treatment, there are also no clear recommendations since there are no data from randomized studies. If perioperative chemotherapy is considered in daily practice, gemcitabine/cisplatin regimen is often chosen and occasionally dd-MVAC. The aim of this study is to explore feasibility of UTUC treatments based in real world data in various European countries. Patients who fulfil good prognostic factors (inclusion criteria for treatment randomization) will be allocated to neo-adjuvant (Arm B) or adjuvant (Arm C) chemotherapy (receiving 3 cycles of gemcitabine/cisplatin or dose dense Methotrexate, Vinblastine, Adriamycin, and Cisplatin (MVAC). Patients who don't fulfil criteria for treatment randomization will undergo Radical nephroureterectomy (RNU) only (Arm A). Patients will be followed up for 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Upper Tract Urothelial Carcinoma
Keywords
UTUC, Upper Tract Urothelial Carcinoma, Neoadjuvant chemotherapy, Adjuvant chemotherapy, Radical nephroureterectomy

7. Study Design

Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Radical nephro-ureterectomy (RNU)
Arm Type
Other
Arm Description
Patients who dont fulfil inclusion criteria for chemotherapy treatment randomization (poor renal function: Glomerular Filtration Rate (GFR) <55 ml/min or unfit for cisplatin-based chemotherapy)
Arm Title
Gemcitabine/Cisplatin plus RNU
Arm Type
Other
Arm Description
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks before surgery
Arm Title
RNU plus Gemcitabine/Cisplatin
Arm Type
Other
Arm Description
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of Gemcitabine (1000 mg/m2) + Cisplatin (70 mg/m2) every 3 weeks after surgery
Arm Title
M-VAC protocol plus RNU
Arm Type
Other
Arm Description
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) before surgery
Arm Title
RNU plus M-VAC protocol
Arm Type
Other
Arm Description
Patients who fulfil inclusion criteria for cisplatinum-based chemotherapy (renal function: GRF > or = 55 ml/min) receiving 3 cycles of MVAC every 2 weeks (Methotrexate (30 mg /m²) , Vinblastine (3 mg /m²) , Adriamycin (30 mg /m²) , and Cisplatin (70 mg /m²) after surgery
Intervention Type
Procedure
Intervention Name(s)
RNU
Other Intervention Name(s)
Radical nephro-ureterectomy
Intervention Description
Radical surgical removal by open or laparoscopic access
Intervention Type
Drug
Intervention Name(s)
Gemcitabine/Cisplatin
Other Intervention Name(s)
Gemcitabine plus Cisplatin
Intervention Description
Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1
Intervention Type
Drug
Intervention Name(s)
M-VAC Protocol
Other Intervention Name(s)
DD MVAC
Intervention Description
Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2
Primary Outcome Measure Information:
Title
Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
Description
Percentage of patients randomised to adjuvant or neo-adjuvant treatment
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Disease Free Survival (DFS)
Description
time from randomisation to local recurrence or distant metastasis
Time Frame
1-2 years
Title
Overall Survival (OS)
Description
time from randomisation to death for any cause different from urothelial carcinoma
Time Frame
1-2 years
Title
Cancer-Specific Survival (CSS)
Description
time from randomisation to death from urothelial carcinoma
Time Frame
1-2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent Age > 18 years Histological and radiological defined UTUC: Histologically-confirmed diagnosis of predominantly urothelial carcinoma of the upper urinary tract Patients with UTUC cT2-pT4 cN0-N1 M0 (TNM classification) Women with negative serum pregnancy test within 14 days of first dose of study treatment and agreement to use effective contraception Patients without bladder cancer or with concomitant non muscle invasive bladder cancer Adequate organ system function defined as follows: Hematologic: Absolute neutrophil count (ANC) 1.5 X 109/L; Haemoglobin 5.6 mmol/L (9.02g/dL); Platelets 100 X 109/L; Prothrombin time (PT) or international normalized ratio (INR)b 1.2 X ULN; Activated partial thromboplastin time (aPTT)1.2 X Upper limit of normal (ULN). Hepatic: Total bilirubin 1.5 X ULN; Alanine amino transferase (ALT) and Aspartate aminotransferase (AST) 2.5 X ULN. Renal: GRF <or> 55 ml/min: Electrolytes: potassium and calcium: within normal limits. CT scan of the chest, abdomen and pelvis and Bone scan without evidence of distant metastasis Exclusion Criteria: Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma. History of cardiovascular conditions within the past 6 months. Incidentally found asymptomatic pulmonary embolism (PE) or recent deep vein thrombosis (DVT) is not an exclusion criteria but requires anticoagulation treatment. Any major contraindication to a surgical procedure. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. Active infection contraindicating chemotherapy Other active neoplasms. Patients with in situ cervical carcinoma, non-melanoma skin cancer or prostate cancer T1 Gleason <7, Prostate specific antigen (PSA) <10. Patients with past medical history of cancer can be included if diagnosed at least 4 years ago. Concomitant muscle invasive bladder cancer Patients who have been or still are on methotrexate treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cristina Alvarez, MSc, PhD
Phone
+31(0)715264109
Email
m.c.alvarez@lumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susanne Osanto, MD, PhD
Organizational Affiliation
Leiden University Medical Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Radboud University Medical Centre
City
Nijmegen
State/Province
Gelderland
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
T Van der Heijden
Facility Name
Leiden University Medical Centre
City
Leiden
State/Province
South Holland
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S Osanto
Facility Name
Alrijne Ziekenhuis
City
Leiderdorp
State/Province
South-Holland
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C Goossens-Laan
Facility Name
Canisius Wilhelmina Ziekenhuis
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
R Somford
Facility Name
Haukeland University Hospital
City
Bergen
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C Beisland
Facility Name
Complejo Hospitalario Universitario A Coruña
City
A Coruña
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Molina
Facility Name
Hospital Universitario German Trias i Pujol
City
Badalona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Alves
Facility Name
Fundacion Puigvert
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J Palou
Facility Name
Hospital Clinico de Barcelona
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Ribal
Facility Name
Hospital San Pau
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
P Maroto
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Gonzalez
Facility Name
Hospital Universitario de Basurto
City
Bilbao
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Anton
Facility Name
Hospital Universitari de Girona Doctor Josep Trueta
City
Gerona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Comet
Facility Name
Hospital Universitario Clínico San Cecilio
City
Granada
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Arrabal
Facility Name
Hospital de Jerez
City
Jerez De La Frontera
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Amores
Facility Name
Hospital Complex Insular-Materno Infantil
City
Las Palmas
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Gómez de Liaño
Facility Name
Clinica Universitaria de Navarra
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Villacampa
Facility Name
Fundacion Jimenez Diaz
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Buendia
Facility Name
Hospital ramón y Cajal
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Burgos
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Alvarez-Maestro
Facility Name
Hospital Clinico Universitario Virgen de la Arrixaca
City
Murcia
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Lopez-Cubillana
Facility Name
Hospital General Universitario Morales Meseguer
City
Murcia
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Fernandez Aparicio
Facility Name
Complejo Hospitalario de Navarra
City
Pamplona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Montesino
Facility Name
Hospital Parc Taulí
City
Sabadell
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Gallardo
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Gomez Veiga
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Campos Juanatey
Facility Name
Hospital Virgen del Rocio
City
Sevilla
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Osman
Facility Name
Fundacion Instituto Valenciano de Oncologia
City
Valencia
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Climent
Facility Name
Hospital Clinico Universitario Lozano Blesa
City
Zaragoza
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Rioja

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
The results obtained in this study will be disseminated and published
Citations:
PubMed Identifier
33168398
Citation
Hird AE, Magee DE, Cheung DC, Sander B, Sridhar S, Nam RK, Kulkarni GS. Neoadjuvant Versus Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Microsimulation Model. Clin Genitourin Cancer. 2021 Apr;19(2):e135-e147. doi: 10.1016/j.clgc.2020.10.001. Epub 2020 Oct 13.
Results Reference
derived

Learn more about this trial

Feasibility of Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma

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