Upper Tract Urothelial Carcinoma
Conditions
Keywords
UTUC, Upper Tract Urothelial Carcinoma, Neoadjuvant chemotherapy, Adjuvant chemotherapy, Radical nephroureterectomy
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.
Interventions
PROCEDURERNU
Radical surgical removal by open or laparoscopic access
Gemcitabine (1000 mg/m²) day 1 and 8 and Cisplatin (70 mg/m²) day 1
DRUGM-VAC Protocol
Methotrexate (30 mg /m²) and Vinblastine 3 (mg /m²) day 1; Adriamycin 30 mg /m² and Cisplatin 70 mg /m² in day2
Sponsors
Centre for Human Drug Research, Netherlands
The European Uro-Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of UTUC patients randomized to neo- or adjuvant chemotherapy that is actually able to start and finalize three courses of planned chemotherapy | 6 months | Percentage of patients randomised to adjuvant or neo-adjuvant treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | 1-2 years | time from randomisation to local recurrence or distant metastasis |
| Overall Survival (OS) | 1-2 years | time from randomisation to death for any cause different from urothelial carcinoma |
| Cancer-Specific Survival (CSS) | 1-2 years | time from randomisation to death from urothelial carcinoma |
Countries
Netherlands, Norway, Spain
Contacts
Primary ContactCristina Alvarez, MSc, PhD
Outcome results
None listed