metastatic or locally advanced transitional cell carcinoma of the urothelium MedDRA version: 14.1 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10005084 Term: Bladder transitional cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: JAVLOR
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: VINFLUNINE
CAS Number: 162652-95-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration ty
Sponsors
Associació Per a la Recerca Oncològica (APRO)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -written informed consent -histologically confirmed TCCU (urinary bladder, urethra, ureter or renal pelvis). Patients with mixed histology may be enrolled if TCCU is the predominant component (i.e., > 50% of the histopathology sample) with the exception of neuroendocrine or small cell carcinoma. -advanced disease defined as a locally advanced tumour considered unresectable (T4b), node involvement in the inguinal area or above the aortic bifurcation (that are considered to be distant nodes and so metastasis) or metastasis in distant organs. -The patient should have received one prior platinum-based chemotherapy treatment for locally advanced or stage IV TCCU. Prior platinum-based adjuvant or neoadjuvant therapy is allowed if more than 6 months have elapsed since the end of adjuvant or neoadjuvant therapy till tumour relapse. -at least one measurable tumour lesion (measurable disease, as defined by the RECIST criteria v1.1), for the phase II part of the study. If all sites of measurable disease have been irradiated, one site must have demonstrated growth after irradiation. For phase III part, patients with only non measurable disease are allowed for enrolment. -Age ?18 years. -ECOG PS 0 or 1. -no more than ONE of the following unfavourable risk factors: a)haemoglobin 1.5x109/L c)Serum creatinine ?1.5 times the upper limit of normality (ULN). d)Alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT) and alkaline phosphatase (AP) ?2.5 ×ULN (=65 years) yes F.1.3.1 Number of subjects for this age range 186
Exclusion criteria
Exclusion criteria: -Patients that have 2 or more of the following unfavourable risk factors: a)Haemoglobin 1 (NCI-CTCAE, Version 4.0) from previous anti-cancer therapy (other than alopecia) -Patients who had undergone major surgery, radiation therapy or treatment with chemotherapy or any investigational agent within 28 days prior to Study day 1. -Evidence of severe or uncontrolled systemic disease or any concurrent condition (including uncontrolled diabetes mellitus) which in the Investigator?s opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol. -History of another neoplasm. Patients with prior history of either non-metastatic non melanoma skin cancers; carcinoma in situ of the cervix; or cancer cured by surgery, small field radiation or chemotherapy ?3 years prior to randomisation; or treated patients with early stage and low risk prostate cancer (?pT2 N0 M0, Gleason ?6 and Prostate-specific antigen [PSA] ?0.5 ng/mL) at study entry will be eligible. -History of hypersensitivity reactions to taxanes (docetaxel) (cabazitaxel specific criteria), vinca alkaloids (vinflunine specific criteria) or to any of the formulation excipients, including polysorbate 80 (cabazitaxel specific criteria). -Patients with clear evidence or symptoms of central nervous system metastasis (cabazitaxel specific criteria). -Clinically significant cardiac condition demonstrated by myocardial infarction or thromboembolic events in the 6 months prior to the study treatment initiation, serious or unstable angina pectoris, New York Heart Association (NYHA) class III or IV congestive heart failure, or left ventricular ejection fraction (LVEF) <50% at baseline (see Appendix VI) (vinflunine specific criteria). -Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (a one week wash-out period is necessary for patients who are already on these treatments)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase II part: -efficacy of cabazitaxel compared to vinflunine in terms of improved objective response rate (ORR) of subjects with metastatic or locally advanced previously treated TCCU. Phase III part: -efficacy of cabazitaxel compared to vinflunine in terms of improved OS of subjects with metastatic or locally advanced, previously treated TCCU.;Secondary Objective: PHASE II part - efficacy of cabazitaxel compared to vinflunine in terms of improved progression-free survival (PFS) and OS - safety profile and tolerability of cabazitaxel PHASE III part - efficacy of cabazitaxel compared to vinflunine in terms of improved ORR and PFS - safety profile and tolerability of cabazitaxel;Primary end point(s): PHASE II part: -ORR, which includes the sum of the complete and partial responses (CR+PR) PHASE III part: -OS;Timepoint(s) of evaluation of this end point: PHASE II part: -ORR; at the end of phase II part (see protocol) PHASE III part: -OS; at the momment of the death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PHASE II part: -PFS -OS -Adverse events PHASE III part: -ORR -PFS -AEs;Timepoint(s) of evaluation of this end point: PHASE II part: -PFS; when progression occurs -OS; at the momment of the death -Adverse events; at the end of phase II part (see protocol) PHASE III part: -ORR: at the end of the sudy (see protocol) -PFS; when progression occurs -AEs; at the end of the study | — |
Countries
Netherlands, Spain
Contacts
Public ContactInmaculada Musté
Per a la Recerca Oncològica (APRO)
Outcome results
None listed