- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02969083
Feasibility of Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma (URANUS)
Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Cristina Alvarez, MSc, PhD
- Phone Number: +31(0)715264109
- Email: m.c.alvarez@lumc.nl
Study Locations
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Nijmegen, Netherlands
- Recruiting
- Canisius Wilhelmina Ziekenhuis
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Contact:
- R Somford
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Gelderland
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Nijmegen, Gelderland, Netherlands
- Recruiting
- Radboud university medical centre
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Contact:
- T Van der Heijden
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South Holland
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Leiden, South Holland, Netherlands
- Recruiting
- Leiden University Medical Centre
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Contact:
- S Osanto
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South-Holland
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Leiderdorp, South-Holland, Netherlands
- Recruiting
- Alrijne Ziekenhuis
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Contact:
- C Goossens-Laan
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Bergen, Norway
- Recruiting
- Haukeland University Hospital
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Contact:
- C Beisland
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-
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A Coruña, Spain
- Not yet recruiting
- Complejo Hospitalario Universitario A Coruña
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Contact:
- Dr. Molina
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Badalona, Spain
- Recruiting
- Hospital Universitario German Trias i Pujol
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Contact:
- Dr. Alves
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Barcelona, Spain
- Not yet recruiting
- Hospital Universitario Vall d'Hebron
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Contact:
- Dr. Gonzalez
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Barcelona, Spain
- Recruiting
- Fundacion Puigvert
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Contact:
- J Palou
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Barcelona, Spain
- Not yet recruiting
- Hospital Clínico de Barcelona
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Contact:
- Dr. Ribal
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Barcelona, Spain
- Recruiting
- Hospital San Pau
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Contact:
- P Maroto
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Bilbao, Spain
- Not yet recruiting
- Hospital Universitario de Basurto
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Contact:
- Dr. Anton
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Gerona, Spain
- Recruiting
- Hospital Universitari de Girona Doctor Josep Trueta
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Contact:
- Dr. Comet
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Granada, Spain
- Recruiting
- Hospital Universitario Clínico San Cecilio
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Contact:
- Dr. Arrabal
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Jerez De La Frontera, Spain
- Not yet recruiting
- Hospital de Jerez
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Contact:
- Dr. Amores
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Las Palmas, Spain
- Not yet recruiting
- Hospital Complex Insular-Materno Infantil
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Contact:
- Dr. Gómez de Liaño
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Madrid, Spain
- Recruiting
- Hospital Universitario La Paz
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Contact:
- Dr. Alvarez-Maestro
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Madrid, Spain
- Recruiting
- Clinica Universitaria de Navarra
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Contact:
- Dr. Villacampa
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Madrid, Spain
- Recruiting
- Hospital Ramon y Cajal
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Contact:
- Dr. Burgos
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Madrid, Spain
- Not yet recruiting
- Fundación Jiménez Díaz
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Contact:
- Dr. Buendia
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Murcia, Spain
- Recruiting
- Hospital Clínico Universitario Virgen de la Arrixaca
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Contact:
- Dr. Lopez-Cubillana
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Murcia, Spain
- Not yet recruiting
- Hospital General Universitario Morales Meseguer
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Contact:
- Dr. Fernandez Aparicio
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Pamplona, Spain
- Recruiting
- Complejo Hospitalario de Navarra
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Contact:
- Dr. Montesino
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Sabadell, Spain
- Recruiting
- Hospital Parc Taulí
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Contact:
- Dr. Gallardo
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Salamanca, Spain
- Recruiting
- Hospital Universitario de Salamanca
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Contact:
- Dr. Gomez Veiga
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Santander, Spain
- Recruiting
- Hospital Universitario Marques de Valdecilla
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Contact:
- Dr. Campos Juanatey
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Sevilla, Spain
- Recruiting
- Hospital Virgen del Rocío
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Contact:
- Dr. Osman
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Valencia, Spain
- Not yet recruiting
- Fundación Instituto Valenciano de Oncología
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Contact:
- Dr. Climent
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Zaragoza, Spain
- Not yet recruiting
- Hospital Clinico Universitario Lozano Blesa
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Contact:
- Dr. Rioja
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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
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:
|
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:
Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1
Other Names:
|
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:
Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1
Other Names:
|
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:
Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2
Other Names:
|
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:
Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2
Other Names:
|
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
Sponsor
Collaborators
Investigators
- Principal Investigator: Susanne Osanto, MD, PhD, Leiden University Medical Centre
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EudraCT 2016-004017-27
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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