A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 3
- 主要终点
- Maximum Tolerated Dose (MTD) PXD101
研究概览
简要总结
Open-label, multicentre, dose-escalation Phase I/II study to evaluate safety, efficacy, pharmacodynamics, and pharmacokinetics of the combination of PXD101 with doxorubicin administered q 3 weeks in patients with advanced solid tumours. Once the Maximum Tolerable Dose has been established, up to a total of 20-40 patients with Soft Tissue Sarcoma may be enrolled at the MTD dose level to examine efficacy and safety in this specific patient population. The trial is stopped if no more than 2 responses are seen among the first 20 of these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Signed consent of an IEC (Independent Ethics Committee)-approved Information consent form
- •A. For the dose escalation phase: Patients with histological or cytological confirmed solid tumours (including sarcomas), for which there is no known curative therapy B. For the MTD expansion phase: Patients with an established diagnosis of soft tissue sarcoma in need of first line chemotherapy and with measurable disease
- •Performance status (ECOG) ≤ 2
- •Life expectancy of at least 3 months
- •Age ≥ 18 years
- •Acceptable liver, renal and bone marrow function including the following:
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST ([Aspartate Amino Transferase]](SGOT), ALT (SGPT) and Alkaline Phosphatase ≤ 3 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed)
- •Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
- •Leucocytes > 2.5 x 109/ L, neutrophils > 1.0 x 109/L, platelets > 100 x 109/L
- •Haemoglobin > 9.0 g/dL or > 5.6 mmol/l
- •Acceptable coagulation status: PT and APTT ([activated partial thromboplastin time ]) within ≤ 1.5 times upper limit of normal or in the therapeutic range if on anticoagulation.
- •A negative pregnancy test for women of childbearing potential. For men and women of child producing potential, the use of effective contraceptive methods during the study is required
- •Serum potassium within normal range
排除标准
- •Treatment with investigational agents within the last 4 weeks
- •Prior anticancer therapy, within the last 3 weeks of trial dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy
- •Co-existing active infection or any co-existing medical condition likely to interfere with trial procedures, including significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, or evidence of ischemia on ECG, marked baseline prolongation of QT/QTc ([corrected QT interval ]) interval, e.g., repeated demonstration of a QTc interval > 500 msec; Long QT Syndrome; the required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes.
- •Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
- •Concurrent second malignancy
- •History of hypersensitivity to doxorubicin
- •A. For dose escalation phase: More than two prior doses of anthracycline, more than three prior lines of chemotherapy given for metastatic disease B. For MTD expansion phase: Prior chemotherapy
- •Bowel obstruction or impending bowel obstruction
- •Known HIV positivity
- •LVEF ([left ventricular ejection fraction]) below normal range (45% by MUGA)
- •Presence of metastatic disease that, in the opinion of the investigator, would require palliative treatment within 4 weeks of enrolment
研究组 & 干预措施
Experimental: PXD101 and doxorubicin (BelDox)
5-day PXD101 IV schedule with dose escalation combined with 1 day doxorubicin dose escalation IV
干预措施: PXD101 (Drug)
Experimental: PXD101 and doxorubicin (BelDox)
5-day PXD101 IV schedule with dose escalation combined with 1 day doxorubicin dose escalation IV
干预措施: Doxorubicin (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) PXD101
时间窗: During Cohort 1 to 4, Cycle 1 only, up to 3 weeks
Maximum Tolerated Dose (MTD) of PXD101treatment
Maximum Tolerated Dose (MTD) of Doxorubicin
时间窗: During Cohort 1 to 4, Cycle 1 only, up to 3 weeks
Maximum Tolerated Dose (MTD) of doxorubicin
Dose Limiting Toxicity (DLT)
时间窗: Throughout study
Dose Limiting Toxicity (DLT) of PXD101 and doxorubicin combination treatment
Objective Response (CR and PR)
时间窗: Throughout study, after every 2 cycles
Measured by response rate using the RECIST (Response Evaluation Criteria in Solid Tumors) response criteria (response rate: Complete Response (CR) and Partial Response (PR)) following up to 6 cycles of treatment.
次要结局
- Time to Response(Throughout study, after every 2 cycles)
- Duration of Response(Throughout study, after every 2 cycles)
- Time to Progression(Throughout study, after every 2 cycles)
- Disease Control Rate (CR or PR or SD)(Throughout study, after every 2 cycles)
- Belinostat AUC (Time 0 to Last Measurement)(Cycle 1, Day 4 and Day 5, pre-infusion, at end of infusion and at 5 min, 15 min, 30 min, 1 h, 2 h, 2 h and 15 min, 2 h and 30 min, 3 h, 4 h, 6 h, 8 h and 24 h post infusion)
- Belinostat Cmax(Cycle 1, Day 4 and Day 5, pre-infusion, at end of infusion and at 5 min, 15 min, 30 min, 1 h, 2 h, 2 h and 15 min, 2 h and 30 min, 3 h, 4 h, 6 h, 8 h and 24 h post infusion)
- Belinostat t½(Cycle 1, Day 4 and Day 5, pre-infusion, at end of infusion and at 5 min, 15 min, 30 min, 1 h, 2 h, 2 h and 15 min, 2 h and 30 min, 3 h, 4 h, 6 h, 8 h and 24 h post infusion)