Brief Title
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
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
Study Phase
Phase 2/Phase 3
Study Type
Interventional
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.
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).
Condition
Urothelium Transitional Cell Carcinoma
Intervention
Cabazitaxel
Study Arms / Comparison Groups
Cabazitaxel
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
372
Start Date
October 2012
Completion Date
November 2016
Primary Completion Date
November 2016
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Joaquim Bellmunt, MD/PhD, +34 93 2483137, [email protected]
Location Countries
Netherlands
Location Countries
Netherlands
Administrative Informations
NCT ID
NCT01830231
Organization ID
Secavin-12
Responsible Party
Sponsor
Study Sponsor
Associació per a la Recerca Oncologica, Spain
Study Sponsor
Joaquim Bellmunt, MD/PhD, Principal Investigator, APRO
Verification Date
January 2014