A randomised study of cabazitaxel versus vinflunine in bladder carcinoma.

• Conditions: metastatic or locally advanced transitional cell carcinoma of the urothelium; MedDRA version: 17.1Level: LLTClassification code 10046714Term: Urothelial carcinoma bladderSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.1Level: PTClassification code 10005084Term: Bladder transitional cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-002826-55-NL
• Lead Sponsor: Associació Per a la Recerca Oncològica (APRO)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-01-29
• Last Update Posted: 1 February 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 372

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 <10 g/dL
b)presence of liver metastasis
c)ECOG PS 1
-Life expectancy of at least 12 weeks.
- Adequate hematologic, hepatic, and renal function, defined by:
a)Platelet count ?100 x109/L
b)Absolute neutrophil count (ANC) >1.5x109/L
c)Serum creatinine =1.5 times the upper limit of normality (ULN). If creatinine 1.0 1.5 xULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <50 mL/min should be excluded)
d)Alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT) and alkaline phosphatase (AP) ?2.5 ×ULN (<5 ×ULN in the presence of liver metastasis), and serum total bilirubin ?1.0 ×ULN.
-Females of childbearing potential must have a negative serum pregnancy test within 7 days of study entry. Patients of childbearing potential who participate in this study must use effective contraceptive methods (e.g., abstinence, intrauterine device, oral or injectable contraceptives, a double barrier method or surgical sterility) to prevent pregnancy starting as soon as the informed consent form is signed and continuing for at least 13 weeks after the last dose of the study medication is administered
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 186
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 186

Exclusion Criteria

-Patients that have 2 or more of the following unfavourable risk factors:
a)Haemoglobin <10 g/L
b)Liver metastasis
c)ECOG PS 1.
2)Women who are currently pregnant or breast-feeding.
-Any unresolved non-hematologic AE grade >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 (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)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified