Feasibility of Neo-adjuvant Versus Adjuvant Chemotherapy in Upper Tract Urothelial Carcinoma
- Conditions
- Upper Tract Urothelial Carcinoma
- Interventions
- Registration Number
- NCT02969083
- Lead Sponsor
- The European Uro-Oncology Group
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description RNU plus Gemcitabine/Cisplatin 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 after surgery RNU plus Gemcitabine/Cisplatin 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 M-VAC protocol plus RNU 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 Radical nephro-ureterectomy (RNU) 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) Gemcitabine/Cisplatin plus RNU 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 M-VAC protocol plus RNU 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) before surgery RNU plus M-VAC protocol 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) after surgery RNU plus M-VAC protocol 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 Gemcitabine/Cisplatin plus RNU 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 before surgery
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
Trial Locations
- Locations (29)
Hospital Clinico de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari de Girona Doctor Josep Trueta
🇪🇸Gerona, Spain
Hospital Complex Insular-Materno Infantil
🇪🇸Las Palmas, Spain
Hospital Universitario German Trias i Pujol
🇪🇸Badalona, Spain
Complejo Hospitalario Universitario A Coruña
🇪🇸A Coruña, Spain
Canisius Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Netherlands
Clinica Universitaria de Navarra
🇪🇸Madrid, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸Zaragoza, Spain
Fundacion Puigvert
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸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
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital San Pau
🇪🇸Barcelona, Spain
Hospital Universitario de Basurto
🇪🇸Bilbao, Spain
Hospital General Universitario Morales Meseguer
🇪🇸Murcia, Spain
Alrijne Ziekenhuis
🇳🇱Leiderdorp, South-Holland, Netherlands
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital de Jerez
🇪🇸Jerez De La Frontera, Spain
Hospital ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Clínico San Cecilio
🇪🇸Granada, Spain
Fundacion Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Haukeland University Hospital
🇳🇴Bergen, Norway
Leiden University Medical Centre
🇳🇱Leiden, South Holland, Netherlands
Radboud University Medical Centre
🇳🇱Nijmegen, Gelderland, Netherlands