A Multicentre, Open Label, Early Stopping Design, Proof Of Concept Study With Tasquinimod In Treating Patients With Advanced Or Metastatic Hepatocellular, Ovarian, Renal Cell And Gastric Carcinomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Ipsen
- 入组人数
- 201
- 试验地点
- 24
- 主要终点
- Progression Free Survival (PFS) Rate, Defined as the Percentage of Patients Who Had Neither Progressed Nor Died as Measured by Centrally Analysed RECIST v1.1 (All Cohorts).
研究概览
简要总结
This was an exploratory proof of concept study to determine the clinical activity of tasquinimod in patients with advanced or metastatic hepatocellular carcinoma, ovarian carcinoma, renal cell carcinoma and gastric carcinoma who had progressed after standard therapies.
详细描述
This was an early stopping design, Phase II, open label, exploratory proof of concept study to evaluate the activity of tasquinimod in four independent cohorts of patients with different tumour types (patients with hepatocellular, ovarian, renal cell or gastric carcinoma, each with progressive disease after standard therapies). Patients initially received 0.5 mg/day tasquinimod dose, increasing to 1 mg/day after at least 2 weeks, unless there were any individual patient safety and tolerability concerns. The treatment period continued until patient disease progression, lost to follow-up, withdrawal or death. During the treatment period, initial study visits were at Week 2, 4 and 8 (± 2 days) for the hepatocellular carcinoma, the ovarian carcinoma and the renal cell carcinoma cohorts and at Week 2, 4 and 6 (± 2 days) for the gastric carcinoma cohort, to allow careful safety monitoring and to facilitate the identification of the individually tolerated dose. After Week 8, when most patients should have reached their tolerable dose, visit frequency was decreased as follows: at Week 16 and 24 (± 2 days) for the hepatocellular carcinoma, the ovarian carcinoma and the renal cell carcinoma cohorts; and at Week 12, 18 and 24 (± 2 days) for the gastric carcinoma cohort. Thereafter visits were once every 8 weeks (± 2 days) for all cohorts. An end of study treatment/withdrawal (EoST/WD) Visit was to be performed at least 14 days after the last dose of study treatment, and/or before treatment with any alternative antitumour therapy was started. Patients who stopped study treatment before disease progression were to be followed up with tumour imaging every 8 weeks until disease progression. Each patient was subsequently followed up for survival (by visit or telephone call) every 3 months after the EoST/WD Visit until death, lost to follow-up, or withdrawal of consent, or until all surviving patients had been followed-up for at least 9 months after their last administration of study treatment.
The clinical activity of tasquinimod was evaluated independently in each cohort of patients of the four different tumour types. Data were presented as of the following study cut-off dates:
- Hepatocellular carcinoma cohort: 03 December 2014 (efficacy data); 11 April 2016 (safety data).
- Ovarian carcinoma cohort: 27 November 2013 (efficacy data); 05 October 2015 (safety data).
- Renal cell carcinoma cohort: 04 December 2013.
- Gastric carcinoma cohort: 27 September 2013.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Hepatocellular Carcinoma Cohort
1 capsule of tasquinimod (0.25 mg or 0.5 mg or 1 mg) taken orally each day until disease progression, lost to follow-up, withdrawal or death.
干预措施: Tasquinimod (Drug)
Ovarian Carcinoma Cohort
1 capsule of tasquinimod (0.25 mg or 0.5 mg or 1 mg) taken orally each day until disease progression, lost to follow-up, withdrawal or death.
干预措施: Tasquinimod (Drug)
Renal Cell Carcinoma Cohort
1 capsule of tasquinimod (0.25 mg or 0.5 mg or 1 mg) taken orally each day until disease progression, lost to follow-up, withdrawal or death.
干预措施: Tasquinimod (Drug)
Gastric Carcinoma Cohort
1 capsule of tasquinimod (0.25 mg or 0.5 mg or 1 mg) taken orally each day until disease progression, lost to follow-up, withdrawal or death.
干预措施: Tasquinimod (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Rate, Defined as the Percentage of Patients Who Had Neither Progressed Nor Died as Measured by Centrally Analysed RECIST v1.1 (All Cohorts).
时间窗: Week 12 (Gastric Carcinoma Cohort); Week 16 (Hepatocellular and Renal Cell Carcinoma Cohorts); Week 24 (Ovarian Carcinoma Cohort).
Progression (prog.) defined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as a 20% increase in sum of longest diameter of target lesions,or a measurable increase in a nontarget lesion,or appearance of new lesions. 'Progressed or Died' when time between start of study drug \&first date of the following events was ≤ to analysis timepoint +3 days:1) Disease prog. according to central review using RECIST v1.1:date of disease prog. or if missing,first exam date of the visit showing a disease prog.2) Death due to any cause. 'Neither progressed, nor died' if central assessment by RECIST v1.1 confirmed no disease prog. was observed at the considered timepoint,i.e. time between start of study medication \&last examination/visit date of complete response (CR),partial response (PR) or stable disease (SD) ≥ analysis timepoint 7days.In other cases, such as patient withdrawal due to AEs without tumor assessment proving prog.,the patient was considered as 'not assessable'.
次要结局
- Best Overall Response and Response Rates (All Cohorts) Using RECIST v1.1 (Centrally and Locally Analysed).(Every 6 weeks until Week 24, thereafter, every 8 weeks until disease progression, up to 36 months (gastric carcinoma cohort); every 8 weeks until disease progression, up to 36 months (all other cohorts).)
- Best Overall Response and Response Rate Based on Choi Criteria (Hepatocellular Carcinoma Cohort).(Every 8 weeks until disease progression, up to 36 months.)
- Time to Progression (TTP) by Choi Criteria (Hepatocellular Carcinoma Cohort).(Every 8 weeks until disease progression, up to 36 months.)
- PFS Rate Measured by Choi Criteria (Hepatocellular Carcinoma Cohort).(Week 16.)
- Clinical Benefit (All Cohorts).(Every 6 weeks until Week 24, thereafter, every 8 weeks until disease progression, up to 36 months (gastric carcinoma cohort); every 8 weeks until disease progression, up to 36 months (all other cohorts).)
- PFS From First Study Treatment to Progression or Death Due to Any Cause Based on Choi Criteria (Hepatocellular Carcinoma Cohort).(Every 8 weeks until disease progression, up to 36 months.)
- PFS From First Study Treatment to Progression or Death Due to Any Cause Based on RECIST v1.1 Criteria (All Cohorts).(Every 6 weeks until Week 24, thereafter, every 8 weeks until disease progression, up to 36 months (gastric carcinoma cohort); every 8 weeks until disease progression, up to 36 months (all other cohorts).)
- TTP by RECIST v1.1 (All Cohorts).(Every 6 weeks until Week 24, thereafter, every 8 weeks until disease progression, up to 36 months (gastric carcinoma cohort); every 8 weeks until disease progression, up to 36 months (all other cohorts).)
- Further Cancer-related Treatment During Follow-up Period (All Cohorts).(16 weeks, Last Patient First Treatment + 16 weeks.)
- Overall Survival (OS), Defined as the Time From First Study Treatment to Death Due to Any Cause (All Cohorts).(Time from first study treatment to death, up to 36 months.)