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

December 12, 2023 updated by: The European Uro-Oncology Group

Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Nijmegen, Netherlands
        • Recruiting
        • Canisius Wilhelmina Ziekenhuis
        • Contact:
          • R Somford
    • Gelderland
      • Nijmegen, Gelderland, Netherlands
        • Recruiting
        • Radboud university medical centre
        • Contact:
          • T Van der Heijden
    • South Holland
      • Leiden, South Holland, Netherlands
        • Recruiting
        • Leiden University Medical Centre
        • Contact:
          • S Osanto
    • South-Holland
      • Leiderdorp, South-Holland, Netherlands
        • Recruiting
        • Alrijne Ziekenhuis
        • Contact:
          • C Goossens-Laan
      • Bergen, Norway
        • Recruiting
        • Haukeland University Hospital
        • Contact:
          • C Beisland
      • A Coruña, Spain
        • Not yet recruiting
        • Complejo Hospitalario Universitario A Coruña
        • Contact:
          • Dr. Molina
      • Badalona, Spain
        • Recruiting
        • Hospital Universitario German Trias i Pujol
        • Contact:
          • Dr. Alves
      • Barcelona, Spain
        • Not yet recruiting
        • Hospital Universitario Vall d'Hebron
        • Contact:
          • Dr. Gonzalez
      • Barcelona, Spain
        • Recruiting
        • Fundacion Puigvert
        • Contact:
          • J Palou
      • Barcelona, Spain
        • Not yet recruiting
        • Hospital Clínico de Barcelona
        • Contact:
          • Dr. Ribal
      • Barcelona, Spain
        • Recruiting
        • Hospital San Pau
        • Contact:
          • P Maroto
      • Bilbao, Spain
        • Not yet recruiting
        • Hospital Universitario de Basurto
        • Contact:
          • Dr. Anton
      • Gerona, Spain
        • Recruiting
        • Hospital Universitari de Girona Doctor Josep Trueta
        • Contact:
          • Dr. Comet
      • Granada, Spain
        • Recruiting
        • Hospital Universitario Clínico San Cecilio
        • Contact:
          • Dr. Arrabal
      • Jerez De La Frontera, Spain
        • Not yet recruiting
        • Hospital de Jerez
        • Contact:
          • Dr. Amores
      • Las Palmas, Spain
        • Not yet recruiting
        • Hospital Complex Insular-Materno Infantil
        • Contact:
          • Dr. Gómez de Liaño
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario La Paz
        • Contact:
          • Dr. Alvarez-Maestro
      • Madrid, Spain
        • Recruiting
        • Clinica Universitaria de Navarra
        • Contact:
          • Dr. Villacampa
      • Madrid, Spain
        • Recruiting
        • Hospital Ramon y Cajal
        • Contact:
          • Dr. Burgos
      • Madrid, Spain
        • Not yet recruiting
        • Fundación Jiménez Díaz
        • Contact:
          • Dr. Buendia
      • Murcia, Spain
        • Recruiting
        • Hospital Clínico Universitario Virgen de la Arrixaca
        • Contact:
          • Dr. Lopez-Cubillana
      • Murcia, Spain
        • Not yet recruiting
        • Hospital General Universitario Morales Meseguer
        • Contact:
          • Dr. Fernandez Aparicio
      • Pamplona, Spain
        • Recruiting
        • Complejo Hospitalario de Navarra
        • Contact:
          • Dr. Montesino
      • Sabadell, Spain
        • Recruiting
        • Hospital Parc Taulí
        • Contact:
          • Dr. Gallardo
      • Salamanca, Spain
        • Recruiting
        • Hospital Universitario de Salamanca
        • Contact:
          • Dr. Gomez Veiga
      • Santander, Spain
        • Recruiting
        • Hospital Universitario Marques de Valdecilla
        • Contact:
          • Dr. Campos Juanatey
      • Sevilla, Spain
        • Recruiting
        • Hospital Virgen del Rocío
        • Contact:
          • Dr. Osman
      • Valencia, Spain
        • Not yet recruiting
        • Fundación Instituto Valenciano de Oncología
        • Contact:
          • Dr. Climent
      • Zaragoza, Spain
        • Not yet recruiting
        • Hospital Clinico Universitario Lozano Blesa
        • Contact:
          • Dr. Rioja

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Radical nephro-ureterectomy (RNU)
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)
Radical surgical removal by open or laparoscopic access
Other Names:
  • Radical nephro-ureterectomy
Other: Gemcitabine/Cisplatin plus RNU
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
Radical surgical removal by open or laparoscopic access
Other Names:
  • Radical nephro-ureterectomy
Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1
Other Names:
  • Gemcitabine plus Cisplatin
Other: RNU plus Gemcitabine/Cisplatin
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
Radical surgical removal by open or laparoscopic access
Other Names:
  • Radical nephro-ureterectomy
Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1
Other Names:
  • Gemcitabine plus Cisplatin
Other: M-VAC protocol plus RNU
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
Radical surgical removal by open or laparoscopic access
Other Names:
  • Radical nephro-ureterectomy
Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2
Other Names:
  • DD MVAC
Other: RNU plus M-VAC protocol
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
Radical surgical removal by open or laparoscopic access
Other Names:
  • Radical nephro-ureterectomy
Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2
Other Names:
  • DD MVAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
Time Frame: 6 months
Percentage of patients randomised to adjuvant or neo-adjuvant treatment
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Free Survival (DFS)
Time Frame: 1-2 years
time from randomisation to local recurrence or distant metastasis
1-2 years
Overall Survival (OS)
Time Frame: 1-2 years
time from randomisation to death for any cause different from urothelial carcinoma
1-2 years
Cancer-Specific Survival (CSS)
Time Frame: 1-2 years
time from randomisation to death from urothelial carcinoma
1-2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Susanne Osanto, MD, PhD, Leiden University Medical Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 28, 2018

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

November 11, 2016

First Submitted That Met QC Criteria

November 17, 2016

First Posted (Estimated)

November 21, 2016

Study Record Updates

Last Update Posted (Estimated)

December 18, 2023

Last Update Submitted That Met QC Criteria

December 12, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The results obtained in this study will be disseminated and published

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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