NCT01030783已完成3 期
A Phase 3, Randomized, Controlled, Multi-Center, Open-Label Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma (TIVO-1)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 517
- 试验地点
- 86
- 主要终点
- Progression-free Survival (PFS) of Subjects With Advanced Renal Cell Cancer (RCC) Randomized to Treatment With Tivozanib or Sorafenib
研究概览
简要总结
This is an open-label, randomized, controlled, multi-national, multi-center, parallel-arm trial comparing tivozanib to sorafenib in subjects with advanced RCC. The study is designed to compare the PFS, OS, ORR, DR, safety and tolerability, and kidney specific symptoms/health outcome measurements of tivozanib and sorafenib.
详细描述
This is an open-label, randomized, controlled, multi-national, multi-center, parallel-arm trial comparing tivozanib to sorafenib in subjects with advanced RCC. The study is designed to compare the PFS, OS, ORR, DR, safety and tolerability, and kidney specific symptoms/health outcome measurements of tivozanib and sorafenib.
Subjects will be randomized (1:1) to treatment with tivozanib or sorafenib and stratified by geographic region (North America/Western Europe, Central/Eastern Europe, or rest of the world); number of prior treatments (0 or 1); and number of metastatic sites/organs involved (1 or ≥ 2).
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
- •≥ 18-years of age.
- •Subjects with recurrent or metastatic RCC.
- •Subjects must have undergone prior nephrectomy (complete or partial) for excision of the primary tumor.
- •Histologically or cytologically confirmed RCC with a clear cell component (subjects with pure papillary cell tumor or other non-clear cell histologies, including collecting duct, medullary, chromophobe, mixed tumor containing predominantly sarcomatoid cells, and unclassified RCC are excluded).
- •Measurable disease per the RECIST criteria Version 1.
- •Treatment naïve subjects or subjects who have received no more than one prior systemic treatment (immunotherapy, including interferon-alfa or interleukin-2 based therapy, chemotherapy, hormonal therapy or an investigational agent) for metastatic RCC. Postoperative or adjuvant systemic therapy will not be counted as a prior therapy unless recurrence is detected within 6 months of completion of treatment, in which case it will be counted as a prior therapy for metastatic disease.
- •ECOG performance status of 0 or 1, and life expectancy ≥ 3 months.
- •If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment.
- •Ability to give written informed consent and comply with protocol requirements.
排除标准
- •Any prior VEGF-directed therapy including VEGF antibody (eg, bevacizumab), VEGF receptor tyrosine kinase inhibitor (eg, sunitinib, sorafenib, axitinib, pazopanib, etc.), VEGF trap (eg, aflibercept), or any other agent or investigational agent targeting the VEGF pathway.
- •Any prior therapy with an agent targeting the mTOR pathway (eg, temsirolimus, everolimus, etc)
- •Primary CNS malignancies or CNS metastases; subjects with previously treated brain metastasis will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
- •Any hematologic abnormalities (as noted in the protocol).
- •Any serum chemistry abnormalities (as noted in the protocol).
- •Significant cardiovascular disease.
- •Non-healing wound, bone fracture, or skin ulcer.
- •Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug.
- •Serious/active infection or infection requiring parenteral antibiotics.
- •Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
- •Significant thromboembolic or vascular disorders within 6 months prior to administration of first dose of study drug.
- •Significant bleeding disorders within 6 months prior to administration of first dose of study drug.
- •Currently active second primary malignancy, including hematologic malignancies (leukemia, lymphoma, multiple myeloma, etc.), other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer and ductal or lobular carcinoma in situ of the breast. Subjects are not considered to have a currently active malignancy if they have completed anti-cancer therapy and have been disease free for >2 years.
- •Pregnant or lactating females.
- •History of genetic or acquired immune suppression disease such as HIV; subjects on immune suppressive therapy for organ transplant.
- •Life-threatening illness or organ system dysfunction compromising safety evaluation.
- •Requirement for hemodialysis or peritoneal dialysis.
- •Inability to swallow pills, malabsorption syndrome or gastrointestinal disease that severely affects the absorption of tivozanib or sorafenib, major resection of the stomach or small bowel, or gastric bypass procedure.
- •Psychiatric disorder or altered mental status precluding informed consent or necessary testing.
- •Sexually active pre-menopausal female subjects (and female partners of male subjects) must use adequate contraceptive measures, while on study and for 50 days after the last dose of study drug. Sexually active male subjects must use adequate contraceptive measures, while on study for at least 90 days after the last dose of drug. All fertile male and female subjects and their partners must agree to use a highly effective method of contraception (including their partner). Effective birth control includes (a) IUD plus one barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm). (Note: Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are not considered effective for this study.)
研究组 & 干预措施
tivozanib (AV-951)
Experimental
干预措施: tivozanib (AV-951) (Drug)
sorafenib
Active Comparator
干预措施: Sorafenib (Drug)
结局指标
主要结局
Progression-free Survival (PFS) of Subjects With Advanced Renal Cell Cancer (RCC) Randomized to Treatment With Tivozanib or Sorafenib
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Disease progression was assessed every 8 weeks.
Progression-Free Survival (PFS) is defined as the time from randomization to first documentation of objective tumor progression (progressive disease) or death due to any reasons whichever comes first. Disease progression per RECIST 1.0 criteria is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
次要结局
- Objective Response Rate (ORR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib(Every 8 weeks from date of randomization until disease progression)
- Overall Survival (OS) of Subjects Randomized to Treatment With Tivozanib or Sorafenib(Date of randomization to date of death)
- Safety and Tolerability of Tivozanib and Sorafenib(From start of treatment therapy to completion of treatment therapy, an average of 11 months)
- Pharmacokinetics (Serum Concentrations) of Tivozanib(Cycle 1, Day 1 (prior to dosing), Cycle 1, Day 15 (prior to dosing), Cycle 2, Day 1 (prior to dosing), and Cycle 2, Day 22-28)
- To Compare Kidney-specific Symptoms and Health Outcome Measurements in Subjects Randomized to Treatment With Tivozanib or Sorafenib(At Day 1 of each 28 day cycle throughout the course of the study, for an average of 11 months per subject)
- Duration of Response (DR) of Subjects Randomized to Treatment With Tivozanib or Sorafenib(Assessed every 8 weeks from date of randomization until date of progression)
研究者
研究点 (86)
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