Urothelium Transitional Cell Carcinoma Clinical Trial
Official title:
A Randomised Phase II/III Study of Cabazitaxel Versus Vinflunine in Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium
Due to limited experience with cabazitaxel in TCCU, the study will be started as a randomised phase II study. The aim of the phase II study is to evaluate if the response rates (CR + PR) are sufficiently high to further study the treatment regimens in a phase III setting.
| Status | Recruiting |
| Enrollment | 372 |
| Est. completion date | November 2016 |
| Est. primary completion date | November 2016 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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. - 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 Response Evaluation Criteria in Solid Tumors (RECIST) criteria v1.1 - =18 years. - ECOG PS 0 or 1. - May have no more than ONE of the following unfavourable risk factors: 1. haemoglobin <10 g/dL 2. presence of liver metastasis 3. ECOG PS 1 - Life expectancy of at least 12 weeks. - Adequate hematologic, hepatic, and renal function, defined by: - Females of childbearing potential must have a negative serum pregnancy test within 7 days of study entry. Exclusion Criteria: - Patients that have 2 or more of the following unfavourable risk factors: 1. Haemoglobin <10 g/L 2. Liver metastasis 3. ECOG PS 1. - Women who are currently pregnant or breast-feeding. - Any unresolved non-hematologic Adverse Event (AE) grade >1 (Common Toxicity Criteria for Adverse Effects (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 - History of another neoplasm. - 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 - clear evidence or symptoms of central nervous system metastasis (cabazitaxel specific criteria). - Clinically significant cardiac condition |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Netherlands | NKI-AvL | Amsterdam | |
| Netherlands | Vumc Amsterdam | Amsterdam | |
| Netherlands | St. Antoniusziekenhuis | Nieuwegein | |
| Netherlands | Erasmus MC Rotterdam | Rotterdam | |
| Spain | Centro Oncologico de Galica | A Coruña | |
| Spain | Complejo Hospitalario Universitario A Coruña | A Coruña | |
| Spain | Hospital del Mar | Barcelona | |
| Spain | Hospital Vall d´Hebron | Barcelona | |
| Spain | Hospital San Pedro de Alcántara | Cáceres | |
| Spain | Hospital General Universitario de Elche | Elche | Alicante |
| Spain | Fundación Jiménez Díaz | Madrid | |
| Spain | Hospital Clínico San Carlos | Madrid | |
| Spain | Hospital Ramón y Cajal | Madrid | |
| Spain | Hospital Universitario 12 de Octubre | Madrid | |
| Spain | Hospital Morales Meseguer | Murcia | |
| Spain | Complejo Hospitalario Universitario Ourense. Hospital Santa María Nai | Ourense | |
| Spain | Hospital Son Llatzer | Palma de Mallorca | |
| Spain | Clínica Universidad de Navarra | Pamplona | Navarra |
| Spain | Hospital Clínico Universitario de Santiago | Santiago de Compostela | A Coruña |
| Spain | Hospital Lzoano Blesa | Zaragoza |
| Lead Sponsor | Collaborator |
|---|---|
| Associació per a la Recerca Oncologica, Spain |
Netherlands, Spain,
Bellmunt J, Choueiri TK, Fougeray R, Schutz FA, Salhi Y, Winquist E, Culine S, von der Maase H, Vaughn DJ, Rosenberg JE. Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens. J Clin Oncol. 2010 Apr 10;28(11):1850-5. doi: 10.1200/JCO.2009.25.4599. Epub 2010 Mar 15. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Phase II main objective: to assess the efficacy of cabazitaxel compared to vinflunine in terms of improved objective response rate (ORR) of subjects with metastatic or locally advanced previously treated TCCU. | Efficacy of cabazitaxel compared to vinflunine on terms of improved objective response rate (ORR) | From date of randomization to disease progression or until 18 months from enrolment. | No |
| Primary | Phase III main objective: To assess the efficacy of cabazitaxel compared to vinflunine in terms of improved overall survival (OS) of subjects with metastatic or locally advanced, previously treated TCCU. | From date of randomization to death from any cause or until 18 months from enrolment. | No | |
| Secondary | Phase II secondary objective: to assess the efficacy of cabazitaxel compared to vinflunine in terms of improved progression-free survival (PFS) and overall survival (OS). | From randomisation to either documented disease progression or death from any cause or until 18 months from enrolment (whichever occurs earlier) | No | |
| Secondary | Phase II secondary objective: safety profile and tolerability of cabazitaxel. It will be determined from the number of Adverse Events reported. | From the date the informed consent is signed up to 30 days after the last dose. | Yes | |
| Secondary | Phase III secondary objective: to assess the efficacy of cabazitaxel compared to vinflunine in terms of improved objetive response rate (ORR) and progression free survival (PFS). | From randomisation to either documented disease progression or death from any cause or until 18 months from enrolment (whichever occurs earlier) | No | |
| Secondary | Phase III secondary objective: safety profile and tolerability of cabazitaxel. It will be determined from the number of Adverse Events reported. | From the date the informed consent is signed up to 30 days after the last dose. | Yes |