An Open Label International Multi-Center Phase 2 Activity And Safety Study Of SU011248 In Patients With Unresectable Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Best Overall Response
研究概览
简要总结
The study will consist of two parts. In Part 1 the study will start enrolling 38 patients and then further 25 patients up to a total of 63 eligible patients. If the study gives good results it can be expanded to a total of 160 patients. SU011248 will be administered orally daily for 4 weeks followed by a 2-week rest at a starting dose of 50 mg [milligrams] with provision for dose reduction based on tolerability. All patients will receive repeated cycles of SU011248 until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival
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
- •Histologically confirmed diagnosis of hepatocellular carcinoma
- •Patients must present with disease not amenable to curative surgery (i.e. either hepatectomy, or liver transplant).
- •Evidence of measurable disease by radiographic technique
- •Adequate organ function.
排除标准
- •Prior treatment with any systemic treatment for liver cancer
- •Presence of clinically relevant ascites
- •Severe hemorrhage <4 weeks of starting study treatment.
- •Diagnosis of second malignancy within last 3 years
- •History of or known brain metastases, spinal cord compression, or carcinomatous meningitis
- •Known human immunodeficiency virus (HIV)
- •Serious acute or chronic illness
- •Current treatment on another clinical trial
- •Pregnant or breastfeeding
研究组 & 干预措施
A
干预措施: Sunitinib (SU011248) (Drug)
结局指标
主要结局
Best Overall Response
时间窗: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
Number of subjects with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)= ≥30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD)= ≥ 20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of ≥ 1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start.
Objective Response (CR or PR)
时间窗: From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter
Number of patients with objective response: confirmed CR or confirmed PR according to RECIST. CR was defined as the disappearance of all target lesions. A PR was defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. To be assigned a status of PR or CR, changes in tumor measurements in patients with responding tumors had to have been confirmed by repeat studies that were performed ≥ 4 weeks after the criteria for response were first met.
次要结局
- Duration of Objective Response (CR or PR)(From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death due to cancer)
- Clinical Benefit Response (CR, PR, or SD With Duration ≥12 Weeks)(From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks on study)
- Best Overall Response of PR or SD With Duration ≥12 Weeks(From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or SD with duration of at least 12 weeks or death due to cancer)
- Progression-Free Survival (Overall ITT)(From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death)
- Progression-Free Survival (ITT Child Pugh Class A Subject Population)(From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter or death)
- Time to Tumor Progression (Overall ITT)(From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter)
- Time to Tumor Progression (ITT Child Pugh Class A Subject Population)(From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter)
- Overall Survival (Overall ITT)(From start of study treatment until death.)
- Overall Survival (ITT Child Pugh Class A Subject Population)(From start of study treatment until death.)
- 1-Year Survival Probability(From start of treatment until Day 28 of Cycle 1, Day 28 of Cycles thereafter up until 1 year.)
- Trough Plasma Concentrations (Ctrough) of Sunitinib(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28))
- Ctrough of SU-012662 (Metabolite of Sunitinib)(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28))
- Ctrough of Total Drug (Sunitinib + SU-012662)(Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28))
- Dose-Corrected Ctrough of Sunitinib(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28))
- Dose-Corrected Ctrough of SU-012662 (Metabolite of Sunitinib)(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28))
- Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)(Cycle 1 (Days 14, 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28))
- Circulating Endothelial Cells (CECs) and Circulating Endothelial Progenitor Cells (CEPs)(Cycle 1 (Days 1, 14), Cycle 2 (Days 1, 28), Cycle 5 (Day 1))
- Tissue Tumor Markers Assessed by Tumor Biopsy(Day 28 of Cycle 1 (optional))
- Plasma Concentration of Vascular Endothelial Growth Factor (VEGF)(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28))
- Plasma Concentration of VEGF-C(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28))
- Plasma Concentration of Soluble VEGF Receptor-2 (sVEGFR-2)(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28))
- Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28))
- Plasma Concentration of Soluble KIT (sKIT)(Cycle 1 (Days 1, 14, 28), Cycle 2 (Days 1, 28), Cycle 5 (Day 28))