Cabazitaxel vs. Vinflunine in Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium (TCCU)

Sponsor

Associació per a la Recerca Oncologica, Spain (Other)

Overall Status

Unknown status

CT.gov ID

NCT01830231

Collaborator

(none)

372

Enrollment

Locations

Arms

Duration (Months)

18.6

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urothelium Transitional Cell Carcinoma	Drug: Cabazitaxel Drug: Vinflunine	Phase 2/Phase 3

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

372 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomised Phase II/III Study of Cabazitaxel Versus Vinflunine in Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium

Study Start Date :

Oct 1, 2012

Anticipated Primary Completion Date :

Nov 1, 2016

Anticipated Study Completion Date :

Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cabazitaxel Cabazitaxel 25 mg/m2 q3w. Cabazitaxel will be given intravenously once every 21 days, starting at a dose of 25 mg/m2 as a 1-hour intravenous infusion	Drug: Cabazitaxel Cabazitaxel, to be given intravenously once every 21 days, starting at a dose of 25 mg/m2 as a 1-hour intravenous infusion. Other Names: Jevtana
Active Comparator: Vinflunine • Vinflunine will be given intravenously once every 21 days, starting at a dose of: 320 mg/m2 in patients aged ≤75 years with PS 0 and no prior pelvic radiation 280 mg/m2 in patients aged >75 - ≤80 years, and/or with PS 1 and/or prior pelvic radiation, 250 mg/m2 in patients aged >80 years.	Drug: Vinflunine Vinflunine, to be given intravenously once every 21 days, as a 20 minute intravenous infusion, starting at a dose of: 320 mg/m2 in patients aged ≤75 years with PS 0 and no prior pelvic radiation, and of 280 mg/m2 in patients aged >75 - ≤80 years or with PS 1 or prior pelvic radiation, 250 mg/m2 in patients aged >80 years. Other Names: Javlor

Arm

Intervention/Treatment

Experimental: Cabazitaxel

Cabazitaxel 25 mg/m2 q3w. Cabazitaxel will be given intravenously once every 21 days, starting at a dose of 25 mg/m2 as a 1-hour intravenous infusion

Drug: Cabazitaxel

Cabazitaxel, to be given intravenously once every 21 days, starting at a dose of 25 mg/m2 as a 1-hour intravenous infusion.

Other Names:

Jevtana

Active Comparator: Vinflunine

• Vinflunine will be given intravenously once every 21 days, starting at a dose of: 320 mg/m2 in patients aged ≤75 years with PS 0 and no prior pelvic radiation 280 mg/m2 in patients aged >75 - ≤80 years, and/or with PS 1 and/or prior pelvic radiation, 250 mg/m2 in patients aged >80 years.

Drug: Vinflunine

Vinflunine, to be given intravenously once every 21 days, as a 20 minute intravenous infusion, starting at a dose of: 320 mg/m2 in patients aged ≤75 years with PS 0 and no prior pelvic radiation, and of 280 mg/m2 in patients aged >75 - ≤80 years or with PS 1 or prior pelvic radiation, 250 mg/m2 in patients aged >80 years.

Other Names:

Javlor

Outcome Measures

Primary Outcome Measures

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. [From date of randomization to disease progression or until 18 months from enrolment.]
Efficacy of cabazitaxel compared to vinflunine on terms of improved objective response rate (ORR)
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.]

Secondary Outcome Measures

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)]
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.]
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)]
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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

haemoglobin <10 g/dL
presence of liver metastasis
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:

Haemoglobin <10 g/L
Liver metastasis
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NKI-AvL	Amsterdam		Netherlands
2	Vumc Amsterdam	Amsterdam		Netherlands
3	St. Antoniusziekenhuis	Nieuwegein		Netherlands
4	Erasmus MC Rotterdam	Rotterdam		Netherlands
5	Hospital Clínico Universitario de Santiago	Santiago de Compostela	A Coruña	Spain	15706
6	Hospital General Universitario de Elche	Elche	Alicante	Spain	03203
7	Clínica Universidad de Navarra	Pamplona	Navarra	Spain	31008
8	Complejo Hospitalario Universitario A Coruña	A Coruña		Spain	15006
9	Centro Oncologico de Galica	A Coruña		Spain	15009
10	Hospital del Mar	Barcelona		Spain	08003
11	Hospital Vall d´Hebron	Barcelona		Spain	08035
12	Hospital San Pedro de Alcántara	Cáceres		Spain	10003
13	Hospital Ramón y Cajal	Madrid		Spain	28034
14	Fundación Jiménez Díaz	Madrid		Spain	28040
15	Hospital Clínico San Carlos	Madrid		Spain
16	Hospital Universitario 12 de Octubre	Madrid		Spain
17	Hospital Morales Meseguer	Murcia		Spain	30008
18	Complejo Hospitalario Universitario Ourense. Hospital Santa María Nai	Ourense		Spain	32005
19	Hospital Son Llatzer	Palma de Mallorca		Spain	07198
20	Hospital Lzoano Blesa	Zaragoza		Spain	50009