Cabazitaxel vs. Vinflunine in Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium (TCCU)
Information source: Associació per a la Recerca Oncologica, Spain
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Urothelium Transitional Cell Carcinoma
Intervention: Cabazitaxel (Drug); Vinflunine (Drug)
Phase: Phase 2/Phase 3
Status: Recruiting
Sponsored by: Associació per a la Recerca Oncologica, Spain Official(s) and/or principal investigator(s): Joaquim Bellmunt, MD/PhD, Principal Investigator, Affiliation: APRO
Overall contact: Joaquim Bellmunt, MD/PhD, Phone: +34 93 2483137, Email: jbellmunt@parcdesalutmar.cat
Summary
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.
Clinical Details
Official title: A Randomised Phase II/III Study of Cabazitaxel Versus Vinflunine in Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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.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.
Secondary outcome: 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).Phase II secondary objective: safety profile and tolerability of cabazitaxel. It will be determined from the number of Adverse Events reported. 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). Phase III secondary objective: safety profile and tolerability of cabazitaxel. It will be determined from the number of Adverse Events reported.
Detailed description:
Once it is confirmed that the subjects fulfil the eligibility criteria and have signed the
informed consent, they will be randomised to receive treatment based on cabazitaxel or
vinflunine according to the following study schema:
(Randomize 1: 1)
- Cabazitaxel 25 mg/m2 q3w
- Vinflunine 250-320 mg/m2 q3w
Random assignment of treatment will be stratified by the presence of 0 versus 1 of the
following unfavourable prognostic risk factors proposed recently by Bellmunt et al. (1):
- Eastern Cooperative Oncology Group (ECOG) PS 1.
- Anaemia with Hb <10 g/dL.
- Presence of liver metastases.
All patients enrolled in the study will receive a cycle of treatment with the study
medication (cabazitaxel or vinflunine) every 21 days until disease progression or
intolerable/unacceptable toxicity. Tumour evaluations will be scheduled every 6 weeks until
progression
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
- 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
Locations and Contacts
Joaquim Bellmunt, MD/PhD, Phone: +34 93 2483137, Email: jbellmunt@parcdesalutmar.cat
NKI-AvL, Amsterdam, Netherlands; Recruiting Martijn Kerst, MD, Principal Investigator
Vumc Amsterdam, Amsterdam, Netherlands; Not yet recruiting van den Eertwegh, MD, Principal Investigator
St. Antoniusziekenhuis, Nieuwegein, Netherlands; Recruiting Maartje Los, MD, Principal Investigator
Erasmus MC Rotterdam, Rotterdam, Netherlands; Recruiting Ronald De witt, MD, PHD, Principal Investigator
Centro Oncologico de Galica, A Coruña 15009, Spain; Recruiting Ana Medina, MD, Principal Investigator
Complejo Hospitalario Universitario A Coruña, A Coruña 15006, Spain; Recruiting Luis Miguel Antón Aparicio, MD, Principal Investigator
Hospital del Mar, Barcelona 08003, Spain; Recruiting Joaquim Bellmunt, MD/PhD Joaquim Bellmunt, MD, PhD, Principal Investigator
Hospital Vall d´Hebron, Barcelona 08035, Spain; Recruiting Phone: 93 274 61 00 Rafael Morales, MD, Principal Investigator
Hospital San Pedro de Alcántara, Cáceres 10003, Spain; Recruiting Ricardo Collado, Principal Investigator
FundaciĂłn JimĂ©nez DĂaz, Madrid 28040, Spain; Recruiting Gustavo Rubio, Principal Investigator
Hospital ClĂnico San Carlos, Madrid, Spain; Not yet recruiting JosĂ© Luis González, MD, Principal Investigator
Hospital RamĂłn y Cajal, Madrid 28034, Spain; Recruiting Enrique Grande, MD, Principal Investigator
Hospital Universitario 12 de Octubre, Madrid, Spain; Not yet recruiting Daniel Castellano, MD, Principal Investigator
Hospital Morales Meseguer, Murcia 30008, Spain; Recruiting Enrique González, Principal Investigator
Complejo Hospitalario Universitario Ourense. Hospital Santa MarĂa Nai, Ourense 32005, Spain; Recruiting Ovidio Fernández, MD, Principal Investigator
Hospital Son Llatzer, Palma de Mallorca 07198, Spain; Recruiting Maria Belén González, MD, Principal Investigator
Hospital Lzoano Blesa, Zaragoza 50009, Spain; Recruiting Eduardo Pujol, MD, Principal Investigator
Hospital ClĂnico Universitario de Santiago, Santiago de Compostela, A Coruña 15706, Spain; Recruiting Urbano Anido, Principal Investigator
Hospital General Universitario de Elche, Elche, Alicante 03203, Spain; Recruiting Federico J. Vázquez, Principal Investigator
ClĂnica Universidad de Navarra, Pamplona, Navarra 31008, Spain; Recruiting Jose L. PĂ©rez, Principal Investigator
Additional Information
Related publications: 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.
Starting date: October 2012
Last updated: January 27, 2014
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