Clinical trial NCT02969083: Feasibility of Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma
Official title: Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma: A Feasibility Phase II Randomized Clinical Trial ("URANUS")"
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Upper Tract Urothelial Carcinoma
Keywords: UTUC
Upper Tract Urothelial Carcinoma
Neoadjuvant chemotherapy
Adjuvant chemotherapy
Radical nephroureterectomy
Lead sponsor: The European Uro-Oncology Group
Sponsor class: OTHER
Collaborators: name: Centre for Human Drug Research, Netherlands
First posted: 2016-11-21
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy
timeFrame: 6 months
Secondary outcomes:
measure: Disease Free Survival (DFS)
timeFrame: 1-2 years
measure: Overall Survival (OS)
timeFrame: 1-2 years
measure: Cancer-Specific Survival (CSS)
timeFrame: 1-2 years
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
state: Gelderland
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
state: South Holland
city: Leiderdorp
country: Netherlands
facility: Alrijne Ziekenhuis
state: South-Holland
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Badalona
country: Spain
facility: Hospital Universitario German Trias i Pujol
city: Barcelona
country: Spain
facility: Fundacion Puigvert
city: Barcelona
country: Spain
facility: Hospital Clinico de Barcelona
city: Barcelona
country: Spain
facility: Hospital San Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
city: Gerona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Jerez De La Frontera
country: Spain
facility: Hospital de Jerez
city: Las Palmas
country: Spain
facility: Hospital Complex Insular-Materno Infantil
city: Madrid
country: Spain
facility: Clinica Universitaria de Navarra
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Sabadell
country: Spain
facility: Hospital Parc Taulí
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
Study officials:
affiliation: Leiden University Medical Centre
name: Susanne Osanto, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.