Locally advanced or Metastatic urothelial carcinoma MedDRA version: 18.1 Level: LLT Classification code 10046721 Term: Urothelial carcinoma bladder stage III System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10046723 Term: Urothelial carcinoma ureter System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification c
Conditions
Interventions
Trade Name: Javlor
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: VINFLUNINE
CAS Number: 162652-95-1
Trade Name: Carboplatin
Pharmaceutical Form: Concentr
Sponsors
Department of Oncology, Karolinska University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Signed informed consent. •Histological or cytological confirmed transitional cell carcinoma of the urothelial tract (mixed histology including transitional cell carcinoma are allowed). •Non-curable unresectable (T4b), locally advanced (lymph node positive (N+)) or metastatic (M1) urothelial carcinoma (including renal pelvic tumours, ureteral tumours, urinary bladder tumours and urethral primary tumours). •No prior antineoplastic chemotherapy or other anti-cancer drugs. Patients who have received neoadjuvant or adjuvant platinum containing chemotherapy and who are diagnosed with loco regional recurrent or metastatic disease after 6 months are eligible. •Creatinine clearance 30 – 60 ml/min (measured by Iohexol or Cr-EDTA technique) •ECOG/WHO Performance Status (PS) 0-1. •= 4 weeks since prior major surgery, = 2 weeks since prior minor surgery (i.e. TUR-B) and = 1 week since prior radiation therapy. •Measurable and/or non-measurable disease using the RECIST v 1:1 criteria defined as: -Measurable disease: lesions that can be measured in at least one dimension and which have not been previously irradiated. Longest diameter ?10 mm or lymph nodes =15 mm in short axis with CT scan or MRI -Non-measurable disease: lesions which have not been previously irradiated, longest diameter =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: •Not fulfilling inclusion criteria as described above •Pure non-transitional cell carcinoma of the urothelial. •Pronounced heamaturia in need of repeated blood transfusions, palliative radiotherapy to the bladder or palliative resection (TUR-B). •Impaired bone marrow function defined as WBC 1.5 x upper limit of normal (ULN) and/or ASAT/ALAT > 2.5 x ULN (> 5 x ULN if known liver metastasis). •Electrocardiogram (ECG) with significant modifications suggesting a high risk of occurrence of angina pectoris or high risk of arrhythmia. •Other malignancies, except adequately treated basal carcinoma or squamos cell carcinoma of the skin or in-situ cervix carcinoma or incidental prostate cancer (T1a, Gleason score = 6, PSA 2.9 mmol/L (= grade ? 2 according to CTCAE v 4.0), -Concurrent congestive heart failure NYHA (class III-IV), -Unstable angina pectoris, or myocardial infarction within 6 months and/or poorly controlled hypertension, -QTc > 450 ms at baseline, -Inflammatory bowel disease, -Peripheral neuropathy grade ? 2 according to CTCAE v 4.0, •Patients who require treatment with ketoconazole, flukonazole, itraconazole, ritonavir, amprenavir, indinavir, rifampicine (any potent CYP3A4 inhibitor or inducer) or phenytoine. •Pregnant or lactating women. •Any psychological, familial, sociological, or geographical condition which does not permit protocol compliance and medical follow-up.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression free survival (FPS) of vinflunine/gemcitabine versus carboplatin/gemcitabine in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract unfit for cisplatin based chemotherapy due to impaired renal function.;Secondary Objective: To evaluate the tumour response (ORR), overall survival (OS) and disease control rate (DCR) of vinflunine/gemcitabine versus carboplatin/gemcitabine in patients with locally advanced or metastatic transitional cell carcinoma of the urothelial tract unfit for cisplatin based chemotherapy due to impaired renal function. To assess the safety and toxicity of vinflunine/gemcitabine versus carboplatin/gemcitabine. To investigate and compare Quality of life during treatment with vinflunine/gemcitabine and carboplatin/gemcitabine respectively. ;Primary end point(s): Progression free survival (PFS), (CR + PR + SD) ;Timepoint(s) of evaluation of this end point: Continously evaluation every second cycle (e.g. every sixth week) until progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall response rate (ORR) (ORR = CR + PR) Overall survival (OS) Disease control rate (DCR), (DCR = CR + PR + Stable Disease (SD)), according to RECIST, every 2nd cycle Data on safety (Serious Adverse Events, Adverse Events leading to premature withdrawal) Data on Quality of Life (Quality of Life Questionnaire C30 (QLQ-C30) Version 3.0) ;Timepoint(s) of evaluation of this end point: Continously evaluation. | — |
Countries
Denmark, Finland, Norway, Sweden
Outcome results
None listed