An Extension Treatment Protocol for Subjects Who Have Participated in a Phase 3 Study of Tivozanib vs. Sorafenib in Renal Cell Carcinoma (Protocol AV-951-09-301).
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 277
- 试验地点
- 75
- 主要终点
- Number of Subjects With Adverse Events
研究概览
简要总结
Open-label, multi-center extension treatment protocol to allow access to tivozanib and sorafenib for subjects who have participated on the AV-951-09-301 protocol. Eligible subjects who were randomized to receive sorafenib on AV-951-09-301 and had documented progression of disease will receive a tivozanib dose of 1.5 mg/day. Eligible subjects who were randomized to tivozanib or sorafenib in AV-951-09-301, and displayed clinical benefit and acceptable tolerability to treatment, will continue to receive tivozanib or sorafenib at the same dose and schedule as in AV-951-09-301.
详细描述
This is an extension treatment protocol to allow access to tivozanib or sorafenib for subjects enrolled on AV-951-09-301(parent protocol). Subjects who failed sorafenib on the parent protocol will be offered tivozanib. Subjects who were randomized to tivozanib, and demonstrated clinical benefit and acceptable tolerability will be offered long-term access to tivozanib. Subjects who were randomized to sorafenib, and demonstrated clinical benefit and acceptable tolerability will be offered long-term access to sorafenib. Subjects who continue receiving sorafenib on this protocol and progress will be allowed to cross-over to tivozanib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •The subject must have participated on Protocol AV-951-09-301, and must meet either of the following bulleted criteria:
- •Demonstrated disease progression per RECIST during treatment with sorafenib, OR
- •Demonstrated clinical benefit [complete response (CR), partial response (PR), or stable disease (SD) per RECIST] and acceptable tolerability after treatment with tivozanib or sorafenib on protocol AV-951-09-
- •Eastern Cooperative Oncology Group performance status ≤ 2 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
排除标准
- •Newly identified central nervous system (CNS) malignancies or documented progression of CNS metastases; subjects will be allowed only if the CNS metastases have been adequately treated with radiotherapy or surgery. For subjects receiving steroid therapy for allowed steroid maintenance therapy.
- •Duration since last dose on Protocol AV-951-09-301:
- •For subjects continuing tivozanib or sorafenib (subjects who demonstrated clinical benefit and acceptable tolerability during treatment with tivozanib or sorafenib on protocol AV-951-09-301): more than 2 weeks since last dose of tivozanib or sorafenib.
- •For subjects initiating tivozanib (ie demonstrated disease progression during treatment with sorafenib): more than 4 weeks since last dose of sorafenib. Subjects demonstrating disease progression due to CNS metastasis will be allowed up to 8 weeks since last dose of sorafenib in order to complete treatment for CNS metastasis.
- •Inadequate recovery from any prior surgical procedure or major surgical procedure within 4 weeks prior to administration of first dose of study drug.
- •Any of the following hematologic abnormalities:
- •Hemoglobin < 9.0 g/dL
- •Absolute neutrophil count < 1500 per mm3
- •Platelet count < 75,000 per mm3
- •Prothrombin time or Partial thromboplastin time >1.5 × upper limit of normal (ULN)
- •Any of the following serum chemistry abnormalities:
- •Total bilirubin > 1.5 × ULN (or > 2.5 × ULN for subjects with Gilbert's syndrome)
- •Aspartate aminotransferase or alanine aminotransferase > 2.5 × ULN (or > 5 × ULN for subjects with liver metastasis)
- •Alkaline phosphatase > 2.5 × ULN (or > 5 × ULN for subjects with liver or bone metastasis)
- •Creatinine > 2.0 × ULN
- •Proteinuria > 3+ by urinalysis or urine dipstick
- •If female, pregnant or lactating.
- •Sexually active pre-menopausal female subjects (and female partners of male subjects) must use adequate contraceptive measures, while on study and for at least 50 days after the last dose of study drug. Sexually active male subjects must use adequate contraceptive measures, while on study and for at least 90 days after the last dose of study drug. All fertile male and female subjects,and their partners,must agree to use a highly effective method of contraception. Effective birth control includes (a) Intrauterine device 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).
- •Uncontrolled hypertension: systolic blood pressure > 150 mmHg or diastolic blood pressure >100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 24 hours apart.
- •Unhealed wounds (including active peptic ulcers).
- •Serious/active infection or infection requiring parenteral antibiotics.
- •Life-threatening illness or organ system dysfunction compromising safety evaluation.
- •Psychiatric disorder, altered mental status precluding informed consent or necessary testing.
- •Inability to comply with protocol requirements.
- •Treatment with another anti-cancer therapy or participation in another interventional protocol (excluding AV-951-09-301).
研究组 & 干预措施
Sorafenib crossover to tivozanib.
The subjects who failed sorafenib (had Response Evaluation Criteria in Solid Tumors [RECIST] - defined progressive disease) on the parent protocol AV-951-09-301 will be offered tivozanib hydrochloride on Protocol AV- 951-09-902.
干预措施: Tivozanib (Drug)
Sorafenib crossover to tivozanib.
The subjects who failed sorafenib (had Response Evaluation Criteria in Solid Tumors [RECIST] - defined progressive disease) on the parent protocol AV-951-09-301 will be offered tivozanib hydrochloride on Protocol AV- 951-09-902.
干预措施: Sorafenib (Drug)
First line tivozanib.
The subjects who were randomized to tivozanib (continued from the parent Protocol AV-951-09-301) and demonstrated clinical benefit and acceptable tolerability in Protocol AV-951-09-301.
干预措施: Tivozanib (Drug)
First line sorafenib.
The subjects who were randomized to sorafenib (continued from the parent Protocol AV-951-09-301) and demonstrated clinical benefit and acceptable tolerability were to be offered long-term access to sorafenib.
干预措施: Sorafenib (Drug)
结局指标
主要结局
Number of Subjects With Adverse Events
时间窗: From enrollment assessed up to 3 years of treatment or until follow-up (up to 30 days end-of-trial visit after treatment discontinuation), whichever occurs earlier
Number of subjects with Treatment-Related Adverse Events (AEs) as assessed by Common Terminology Criteria for Adverse Events v3.0
Number of Days Subjects Received Treatment in Each Treatment Arm
时间窗: From enrollment to until all subjects discontinue (due to documented progressive disease [PD] or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
Number of days subjects received treatment who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD
Total Dose Administered to Subjects in Each Treatment Arm (mg)
时间窗: From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
The total dose administered to subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD
Average Daily Dose Administered to Subjects in Each Treatment Arm
时间窗: From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
The average daily dose administered to subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD
Relative Dose Intensity (RDI) of Treatment Administered to Subjects in Each Treatment Arm
时间窗: From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
RDI is defined as 100% times the actual dose intensity divided by the intended dose intensity. The RDI of subjects who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD
Number of Cycles Subjects Received Treatment in Each Treatment Arm
时间窗: From enrollment to until all subjects discontinue (due to documented PD or unacceptable toxicities) or until 3 years after the first subject was enrolled in Protocol AV-951-09-902
Number of cycles subjects received who were from Protocol AV-951-09-301 who either continued on tivozanib in this trial (subjects with first-line experience on tivozanib treatment), who crossed over from sorafenib to tivozanib in this trial (crossover subjects) participated in, and who continued on sorafenib in this trial (subjects with first-line experience on sorafenib treatment). Subjects could be discontinued due to unacceptable toxicities or clinical or documented PD
次要结局
- Duration of Response (DR)(From the first documentation of objective tumor response to the first documentation of objective tumor progression, assessed up to treatment discontinuation or to death due to any reason or maximum up to 3 years, whichever occurs earlier)
- Progression-free Survival (PFS)(From the date of first dose of study drug (tivozanib or sorafenib) in the AV-951-09-902 study to the first documentation of objective tumor progression or death due to any reason or maximum up to 3 years, whichever occurred first)
- Number of Subjects With Objective Response Rate (ORR) Who Continued Treatment With Tivozanib or Sorafenib and Who Received Tivozanib After Failure of Sorafenib(From Day 1 to the end of treatment (EOT) Visit, approximately every 8 weeks)
- Overall Survival (OS)(From the date of first dose of study drug (tivozanib or sorafenib) in the AV-951-09-902 study to death due to any reason or maximum up to 3 years, whichever occurred first)