Clinical trial NCT01830231: Cabazitaxel vs. Vinflunine in Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium (TCCU)
Official title: A Randomised Phase II/III Study of Cabazitaxel Versus Vinflunine in Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Urothelium Transitional Cell Carcinoma
Keywords: TCCU
Vinflunine
Cabazitaxel
Metastatic
Locally advance
Lead sponsor: Associació per a la Recerca Oncologica, Spain
Sponsor class: OTHER
First posted: 2013-04-12
Enrollment: 372
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: 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.
timeFrame: From date of randomization to disease progression or until 18 months from enrolment.
measure: 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.
timeFrame: From date of randomization to death from any cause or until 18 months from enrolment.
Secondary outcomes:
measure: 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).
timeFrame: From randomisation to either documented disease progression or death from any cause or until 18 months from enrolment (whichever occurs earlier)
measure: Phase II secondary objective: safety profile and tolerability of cabazitaxel. It will be determined from the number of Adverse Events reported.
timeFrame: From the date the informed consent is signed up to 30 days after the last dose.
measure: 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).
timeFrame: From randomisation to either documented disease progression or death from any cause or until 18 months from enrolment (whichever occurs earlier)
measure: Phase III secondary objective: safety profile and tolerability of cabazitaxel. It will be determined from the number of Adverse Events reported.
timeFrame: From the date the informed consent is signed up to 30 days after the last dose.
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: NKI-AvL
city: Amsterdam
country: Netherlands
facility: Vumc Amsterdam
city: Nieuwegein
country: Netherlands
facility: St. Antoniusziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC Rotterdam
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
state: A Coruña
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: A Coruña
country: Spain
facility: Centro Oncologico de Galica
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebron
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Murcia
country: Spain
facility: Hospital Morales Meseguer
city: Ourense
country: Spain
facility: Complejo Hospitalario Universitario Ourense. Hospital Santa María Nai
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Zaragoza
country: Spain
facility: Hospital Lzoano Blesa
Study officials:
affiliation: APRO
name: Joaquim Bellmunt, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Bellmunt J, Kerst JM, Vazquez F, Morales-Barrera R, Grande E, Medina A, Gonzalez Graguera MB, Rubio G, Anido U, Fernandez Calvo O, Gonzalez-Billalabeitia E, Van den Eertwegh AJM, Pujol E, Perez-Gracia JL, Gonzalez Larriba JL, Collado R, Los M, Macia S, De Wit R; SOGUG and DUOS. A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN). Ann Oncol. 2017 Jul 1;28(7):1517-1522. doi: 10.1093/annonc/mdx186.