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

NCT ID: NCT02969083

Last Updated: 2023-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-28

Study Completion Date

2025-12-31

Brief Summary

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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

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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.

Conditions

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Upper Tract Urothelial Carcinoma

Keywords

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UTUC Upper Tract Urothelial Carcinoma Neoadjuvant chemotherapy Adjuvant chemotherapy Radical nephroureterectomy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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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)

Group Type OTHER

RNU

Intervention Type PROCEDURE

Radical surgical removal by open or laparoscopic access

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

Group Type OTHER

RNU

Intervention Type PROCEDURE

Radical surgical removal by open or laparoscopic access

Gemcitabine/Cisplatin

Intervention Type DRUG

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

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

Group Type OTHER

RNU

Intervention Type PROCEDURE

Radical surgical removal by open or laparoscopic access

Gemcitabine/Cisplatin

Intervention Type DRUG

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

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

Group Type OTHER

RNU

Intervention Type PROCEDURE

Radical surgical removal by open or laparoscopic access

M-VAC Protocol

Intervention Type DRUG

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

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

Group Type OTHER

RNU

Intervention Type PROCEDURE

Radical surgical removal by open or laparoscopic access

M-VAC Protocol

Intervention Type DRUG

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

Interventions

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RNU

Radical surgical removal by open or laparoscopic access

Intervention Type PROCEDURE

Gemcitabine/Cisplatin

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

Intervention Type DRUG

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

Intervention Type DRUG

Other Intervention Names

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Radical nephro-ureterectomy Gemcitabine plus Cisplatin DD MVAC

Eligibility Criteria

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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.
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre for Human Drug Research, Netherlands

OTHER

Sponsor Role collaborator

The European Uro-Oncology Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susanne Osanto, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Centre

Locations

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Radboud University Medical Centre

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Leiden University Medical Centre

Leiden, South Holland, Netherlands

Site Status RECRUITING

Alrijne Ziekenhuis

Leiderdorp, South Holland, Netherlands

Site Status RECRUITING

Canisius Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Site Status RECRUITING

Haukeland University Hospital

Bergen, , Norway

Site Status RECRUITING

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitario German Trias i Pujol

Badalona, , Spain

Site Status RECRUITING

Fundacion Puigvert

Barcelona, , Spain

Site Status RECRUITING

Hospital Clinico de Barcelona

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Hospital San Pau

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitario de Basurto

Bilbao, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitari de Girona Doctor Josep Trueta

Girona, , Spain

Site Status RECRUITING

Hospital Universitario Clínico San Cecilio

Granada, , Spain

Site Status RECRUITING

Hospital de Jerez

Jerez de la Frontera, , Spain

Site Status NOT_YET_RECRUITING

Hospital Complex Insular-Materno Infantil

Las Palmas, , Spain

Site Status NOT_YET_RECRUITING

Clinica Universitaria de Navarra

Madrid, , Spain

Site Status RECRUITING

Fundacion Jimenez Diaz

Madrid, , Spain

Site Status NOT_YET_RECRUITING

Hospital ramón y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, , Spain

Site Status RECRUITING

Hospital General Universitario Morales Meseguer

Murcia, , Spain

Site Status NOT_YET_RECRUITING

Complejo Hospitalario de Navarra

Pamplona, , Spain

Site Status RECRUITING

Hospital Parc Taulí

Sabadell, , Spain

Site Status RECRUITING

Hospital Universitario de Salamanca

Salamanca, , Spain

Site Status RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status RECRUITING

Hospital Virgen del Rocio

Seville, , Spain

Site Status RECRUITING

Fundacion Instituto Valenciano de Oncologia

Valencia, , Spain

Site Status NOT_YET_RECRUITING

Hospital Clinico Universitario Lozano Blesa

Zaragoza, , Spain

Site Status NOT_YET_RECRUITING

Countries

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Netherlands Norway Spain

Central Contacts

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Cristina Alvarez, MSc, PhD

Role: CONTACT

Phone: +31(0)715264109

Email: [email protected]

Facility Contacts

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T Van der Heijden

Role: primary

S Osanto

Role: primary

C Goossens-Laan

Role: primary

R Somford

Role: primary

C Beisland

Role: primary

Dr. Molina

Role: primary

Dr. Alves

Role: primary

J Palou

Role: primary

Dr. Ribal

Role: primary

P Maroto

Role: primary

Dr. Gonzalez

Role: primary

Dr. Anton

Role: primary

Dr. Comet

Role: primary

Dr. Arrabal

Role: primary

Dr. Amores

Role: primary

Dr. Gómez de Liaño

Role: primary

Dr. Villacampa

Role: primary

Dr. Buendia

Role: primary

Dr. Burgos

Role: primary

Dr. Alvarez-Maestro

Role: primary

Dr. Lopez-Cubillana

Role: primary

Dr. Fernandez Aparicio

Role: primary

Dr. Montesino

Role: primary

Dr. Gallardo

Role: primary

Dr. Gomez Veiga

Role: primary

Dr. Campos Juanatey

Role: primary

Dr. Osman

Role: primary

Dr. Climent

Role: primary

Dr. Rioja

Role: primary

References

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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.

Reference Type DERIVED
PMID: 33168398 (View on PubMed)

Other Identifiers

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EudraCT 2016-004017-27

Identifier Type: -

Identifier Source: org_study_id