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

NCT02969083 | Unknown Phase 2 DMC

• 1 other identifier: EudraCT 2016-004017-27
• Study Type: interventional
• Target: 200
• Locations: 3 countries
• Sites: 29

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.

Conditions

Upper Tract Urothelial Carcinoma

Keywords

UTUC; Upper Tract Urothelial Carcinoma; Neoadjuvant chemotherapy; Adjuvant chemotherapy; Radical nephroureterectomy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Disease Free Survival (DFS)

  1-2 years

• Overall Survival (OS)

  1-2 years

• Cancer-Specific Survival (CSS)

  1-2 years

Study Arms (5)

Radical nephro-ureterectomy (RNU)

OTHER

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)

Procedure: RNU

Gemcitabine/Cisplatin plus RNU

OTHER

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

Procedure: RNU; Drug: Gemcitabine/Cisplatin

RNU plus Gemcitabine/Cisplatin

OTHER

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

Procedure: RNU; Drug: Gemcitabine/Cisplatin

M-VAC protocol plus RNU

OTHER

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

Procedure: RNU; Drug: M-VAC Protocol

RNU plus M-VAC protocol

OTHER

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

Procedure: RNU; Drug: M-VAC Protocol

Interventions

RNU PROCEDURE

Radical surgical removal by open or laparoscopic access

Also known as: Radical nephro-ureterectomy

Gemcitabine/Cisplatin plus RNU; M-VAC protocol plus RNU; RNU plus Gemcitabine/Cisplatin; RNU plus M-VAC protocol; Radical nephro-ureterectomy (RNU)

Gemcitabine/Cisplatin DRUG

Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1

Also known as: Gemcitabine plus Cisplatin

Gemcitabine/Cisplatin plus RNU; RNU plus Gemcitabine/Cisplatin

M-VAC Protocol DRUG

Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2

Also known as: DD MVAC

M-VAC protocol plus RNU; RNU plus M-VAC protocol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Histology of pure adenocarcinoma, pure squamous cell carcinoma, sarcomatoid or predominant small cell carcinoma.
• History of cardiovascular conditions within the past 6 months.
• 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.

Sponsors & Collaborators

• The European Uro-Oncology Group: lead
• Centre for Human Drug Research, Netherlands: collaborator

Study Sites (29)

Radboud University Medical Centre

Nijmegen, Gelderland, Netherlands

RECRUITING

Leiden University Medical Centre

Leiden, South Holland, Netherlands

RECRUITING

Alrijne Ziekenhuis

Leiderdorp, South Holland, Netherlands

RECRUITING

Canisius Wilhelmina Ziekenhuis

Nijmegen, Netherlands

RECRUITING

Haukeland University Hospital

Bergen, Norway

RECRUITING

Complejo Hospitalario Universitario A Coruña

A Coruña, Spain

NOT YET RECRUITING

Hospital Universitario German Trias i Pujol

Badalona, Spain

RECRUITING

Fundacion Puigvert

Barcelona, Spain

RECRUITING

Hospital Clinico de Barcelona

Barcelona, Spain

NOT YET RECRUITING

Hospital San Pau

Barcelona, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, Spain

NOT YET RECRUITING

Hospital Universitario de Basurto

Bilbao, Spain

NOT YET RECRUITING

Hospital Universitari de Girona Doctor Josep Trueta

Girona, Spain

RECRUITING

Hospital Universitario Clínico San Cecilio

Granada, Spain

RECRUITING

Hospital de Jerez

Jerez de la Frontera, Spain

NOT YET RECRUITING

Hospital Complex Insular-Materno Infantil

Las Palmas, Spain

NOT YET RECRUITING

Clinica Universitaria de Navarra

Madrid, Spain

RECRUITING

Fundacion Jimenez Diaz

Madrid, Spain

NOT YET RECRUITING

Hospital ramón y Cajal

Madrid, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Spain

RECRUITING

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, Spain

RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, Spain

NOT YET RECRUITING

Complejo Hospitalario de Navarra

Pamplona, Spain

RECRUITING

Hospital Parc Taulí

Sabadell, Spain

RECRUITING

Hospital Universitario de Salamanca

Salamanca, Spain

RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, Spain

RECRUITING

Hospital Virgen del Rocio

Seville, Spain

RECRUITING

Fundacion Instituto Valenciano de Oncologia

Valencia, Spain

NOT YET RECRUITING

Hospital Clinico Universitario Lozano Blesa

Zaragoza, Spain

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 33168398 DERIVED

MeSH Terms

Interventions

Gemcitabine; Cisplatin; M-VAC protocol

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Susanne Osanto, MD, PhD

  Leiden University Medical Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cristina Alvarez, MSc, PhD

CONTACT

+31(0)715264109; m.c.alvarez@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2016
• First Posted: November 21, 2016
• Study Start: May 28, 2018
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: December 18, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (4); NO (1); ES (24)