A Phase III Trial of Vinflunine Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer Previously Treated With or Resistant to an Anthracycline and Who Are Taxane Resistant.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 770
- 主要终点
- Progression Free Survival
研究概览
简要总结
The increasing use of anthracyclines and taxanes in the adjuvant, neoadjuvant and first-line metastatic settings, led to a raise of patients presenting with metastatic breast cancer after treatment with these agents. Options for the treatment of patients who have progressed after an anthracycline and a taxane are limited. The high level of in-vitro synergy of vinflunine combined with 5-fluorouracil (5-FU) together with the good tolerance and the encouraging response rate observed while combining IV vinflunine to oral capecitabine make it a promising combination to investigate further in a phase III trial. This phase III trial will evaluate the effectiveness and the safety profile of such combination for the treatment of patient with advanced breast cancer previously treated with or resistant to anthracycline and taxane resistant.
详细描述
This multicentre, open-label, randomised, Phase III study will enrol 764 patients with advanced breast cancer who have previously been treated with or are resistant to an anthracycline and who are taxane resistant. Patients will be randomised in a 1:1 ratio to receive vinflunine plus capecitabine (Arm A) or capecitabine alone (Arm B).
Randomisation will be stratified according to a minimization procedure:
- Resistance to anthracyclines ("yes" versus "no"), Relapse ≤ 12 months in the adjuvant or neoadjuvant setting or progression ≤ 4 months in the metastatic setting,
- Karnofsky performance status ("90-100" versus "70-80"),
- Measurable disease ("yes" versus "no"),
- The number of prior lines of chemotherapy in the metastatic setting ("0" versus "1" versus "> 1") and,
- Study site.
Patients randomised in Arm A will receive:
- Vinflunine at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute i.v. infusion and,
- Capecitabine which will be self-administered by the patient in an outpatient setting. Patients will take 825 mg/m² twice daily per os for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest. A cycle of therapy is defined as 3 weeks.
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
- 21 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •female patients
- •21 years of age or older
- •histologically/cytologically confirmed carcinoma of the breast
- •documented locally recurrent or metastatic disease not amenable to curative surgery or radiotherapy
- •either one, two or three prior chemotherapy regimens
- •prior treatments including both an anthracycline and a taxane and patient no longer candidate for these drugs
- •measurable or non-measurable disease according to RECIST 1.1
- •Karnofsky performance score of at least 70 %
- •adequate haematological, hepatic and renal functions
- •ECG without clinically relevant abnormality
排除标准
- •known or clinical evidence of brain metastasis or leptomeningeal involvement
- •pulmonary lymphangitis or symptomatic pleural effusion
- •any serious, concurrent uncontrolled medical disorder
- •history of second primary malignancy
- •preexisting motor/sensory peripheral neuropathy
- •known history of HIV infection
- •prior therapy with capecitabine and/or vinca-alkaloids
- •history of severe hypersensitivity to vinca alkaloids and/or to fluoropyrimidine or contra indication to any of these drugs
- •known or suspected dihydropyrimidine dehydrogenase (DPD) deficiency
- •pregnancy or breast feeding
研究组 & 干预措施
Capecitabine single-agent
Capecitabine at the dose of 825mg/m² per os twice per day each morning and each evening for 14 consecutive days beginning on day 1 of each cycle repeated every 3 weeks (self-administered).
干预措施: Capecitabine (Drug)
Vinflunine plus Capecitabine
Patients received (in combination with capecitabine)
• Vinflunine at the dose of 280 mg/m² and as a 20-minute IV. infusion on day 1 of each cycle repeated every 3 weeks.
干预措施: Vinflunine plus Capecitabine (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: Baseline up to 2 years 7 months
PFS is defined as time from date of randomization to date of the first documentation of objective tumor progression (according to the Independent Response Review Committee (IRC) and based on RECIST version 1.1) or death due to any cause. The PFS was primarily analysed in the Intent-to-treat (ITT) population. Patients lost to follow-up, or without a known record of progression or death at time of analysis had the progression-free survival censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression, whichever occurs last.
次要结局
- Overall Survival(Baseline upto 3 years 10 months)
- Overall Response Rate (ORR)(Baseline upto 2 years 7 months)
- Disease Control Rate(Baseline up to 2 years 7 months)
- Duration of Response(Baseline up to 2 years 7 months)