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

Upper Tract Urothelial Carcinoma Clinical Trial

— URANUS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02969083
• Other study ID #: EudraCT 2016-004017-27
• Status: Recruiting
• Phase: Phase 2
• Start date: May 28, 2018
• Est. completion date: December 2025

Study information

• Verified date: March 2023
• Source: The European Uro-Oncology Group
• Contact: Cristina Alvarez, MSc, PhD
• Phone: +31(0)715264109
• Email: m.c.alvarez[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Upper Tract Urothelial Carcinoma

Intervention

Procedure:
• RNU
Radical surgical removal by open or laparoscopic access

Drug:
• Gemcitabine/Cisplatin
Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1
• M-VAC Protocol
Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Centre	Leiden	South Holland
Netherlands	Alrijne Ziekenhuis	Leiderdorp	South-Holland
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Radboud University Medical Centre	Nijmegen	Gelderland
Norway	Haukeland University Hospital	Bergen
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Universitario German Trias i Pujol	Badalona
Spain	Fundacion Puigvert	Barcelona
Spain	Hospital Clinico de Barcelona	Barcelona
Spain	Hospital San Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario de Basurto	Bilbao
Spain	Hospital Universitari de Girona Doctor Josep Trueta	Gerona
Spain	Hospital Universitario Clínico San Cecilio	Granada
Spain	Hospital de Jerez	Jerez De La Frontera
Spain	Hospital Complex Insular-Materno Infantil	Las Palmas
Spain	Clinica Universitaria de Navarra	Madrid
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital ramón y Cajal	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Clinico Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Hospital Parc Taulí	Sabadell
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Fundacion Instituto Valenciano de Oncologia	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
The European Uro-Oncology Group	Centre for Human Drug Research, Netherlands

Countries where clinical trial is conducted

Netherlands,  Norway,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	6 months
Secondary	Disease Free Survival (DFS)	time from randomisation to local recurrence or distant metastasis	1-2 years
Secondary	Overall Survival (OS)	time from randomisation to death for any cause different from urothelial carcinoma	1-2 years
Secondary	Cancer-Specific Survival (CSS)	time from randomisation to death from urothelial carcinoma	1-2 years