A Randomised Phase II/III Study of Cabazitaxel Versus Vinflunine in Metastatic or Locally Advanced Transitional Cell Carcinoma of the Urothelium
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 372
- 试验地点
- 20
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •May have no more than ONE of the following unfavourable risk factors:
- •haemoglobin <10 g/dL
- •presence of liver metastasis
- •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.
排除标准
- •Patients that have 2 or more of the following unfavourable risk factors:
- •Haemoglobin <10 g/L
- •Liver metastasis
- •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
- •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
研究组 & 干预措施
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
干预措施: Cabazitaxel (Drug)
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.
干预措施: Vinflunine (Drug)
结局指标
主要结局
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.
时间窗: 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.
时间窗: From date of randomization to death from any cause or until 18 months from enrolment.
次要结局
- 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.)
- 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))