A Randomized, Phase 3, Double-blind, Placebo-controlled Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma(RENAVIV)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 413
- 试验地点
- 38
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This is a randomized, Phase 3, double-blind, placebo-controlled study of pazopanib plus abexinostat versus pazopanib plus placebo in patients with locally advanced unresectable or metastatic renal cell carcinoma (RCC).
详细描述
In this randomized, Phase 3, double-blind, placebo-controlled study, patients will be randomized 2:1 to receive either a combination of pazopanib plus abexinostat or pazopanib plus placebo. At the time of disease progression, patient treatment assignment will be unblinded, and those patients randomized to the pazopanib plus placebo treatment arm will have the option of crossing over to receive treatment with a combination of pazopanib plus abexinostat. After providing written informed consent, patients will be screened for study eligibility within 28 days before their first dose of study drug. After screening assessments, patients who are eligible for inclusion in the study will be randomized and receive their first dose of study drug on Cycle 1 Day 1 (C1D1), within 7 days of randomization. A treatment cycle is 28 days in length. Patients may continue to receive study drug until any of the following events: the development of IRC-verified radiographic progression as assessed by RECIST version 1.1, clinical disease progression, unacceptable toxicity, another discontinuation criterion is met, withdrawal of consent, or closure of the study by the sponsor. No maximum duration of therapy has been set.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a double-blind study. The sponsor, investigators, study coordinators, and the patients will be blinded to the study drug (abexinostat/placebo).
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
- •To be enrolled in the study, patients will be required to meet all of the following criteria:
- •Patients aged ≥ 18 years at time of study entry.
- •Patients have histologically confirmed RCC with clear cell component.
- •Patients have locally advanced and unresectable or metastatic disease.
- •Measurable disease as assessed only by the investigator (not verified by IRC) according to RECIST version 1.
- •Patients must not have had any prior vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor treatment in either (neo)adjuvant or locally advanced/metastatic setting. Up to 1 line of prior cytokine or immune checkpoint inhibitor treatment is allowed in either the (neo)adjuvant or metastatic setting provided screening scans indicate progressive disease (PD) during or following completion of treatment.
- •Patients have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Patients have adequate baseline organ function.
- •Patients have adequate baseline hematologic function
- •Patient must be at least 2 weeks from last systemic treatment or dose of radiation prior to date of randomization.
排除标准
- •Patients who meet any of the following criteria at Screening will not be enrolled in the study:
- •Has persistent clinically significant toxicities (Grade ≥ 2; per NCI CTCAE version 5 from previous anticancer therapy (excluding alopecia which is permitted and excluding Grades 2 and 3 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the investigator, and can be managed with available medical therapies).
- •Has untreated central nervous system (CNS) metastases. Patients with treated CNS metastases are eligible provided imaging demonstrates no new or progressive metastases obtained at least 4 weeks following completion of treatment. CNS imaging during Screening is not required unless clinically indicated.
- •Has an additional malignancy requiring treatment within the past 3 years. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, and non-muscle invasive urothelial carcinoma.
- •Poorly controlled hypertension, defined as systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 100 mmHg. Use of anti-hypertensives and rescreening is permitted.
- •A new pulmonary embolism or deep venous thrombosis diagnosed within 3 months prior to randomization.
- •Has a QTcF interval > 480 msec.
- •New York Heart Association Class III or IV congestive heart failure.
- •Use of prohibited medication within 7 days or 5 half-lives, whichever is shorter, prior to first dose of study drug.
研究组 & 干预措施
Pazopanib plus abexinostat
Randomized patients will receive a combination of pazopanib plus abexinostat. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat p.o twice daily (BID) on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of abexinostat at the same time each day.
干预措施: Pazopanib (Drug)
Pazopanib plus abexinostat
Randomized patients will receive a combination of pazopanib plus abexinostat. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat p.o twice daily (BID) on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of abexinostat at the same time each day.
干预措施: Abexinostat (Drug)
Pazopanib plus placebo
Randomized patients will receive a combination of pazopanib plus abexinostat matching placebo. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat matching placebo p.o BID on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of placebo at the same time each day.
干预措施: Pazopanib (Drug)
Pazopanib plus placebo
Randomized patients will receive a combination of pazopanib plus abexinostat matching placebo. The patients will receive pazopanib by mouth (p.o.) daily on Days 1 to 28 of each treatment cycle and will receive abexinostat matching placebo p.o BID on Days 1 to 4, 8 to 11, and 15 to 18 of every 28-day cycle, 2 doses 4 hours apart. Patients will be instructed to take their once- daily oral dose of pazopanib and BID oral dose of placebo at the same time each day.
干预措施: Placebo (Other)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: From randomization date to date of first documentation of progression OR death (up to approximately 4 years).
To compare the PFS between treatment arms. PFS is defined as the time (month) interval between date of randomization and date of radiographic disease progression or death for those without prior evidence of progression, as assessed by blinded Independent Review Committee (IRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
次要结局
- Overall survival (OS)(From progression or end of study, every 3 months follow up until death, patient withdrawal from study follow-up, or study closure, whichever occurs first (up to approximately 4 years).)
- Mean change from Baseline in Functional Assessment of Cancer Therapy Kidney System Index (FKSI-19) scores(First day of treatment Cycle1, Cycle 2, Cycle 6 (each cycle is 28 days in length) until end-of-treatment visit (up to approximately 4 years).)
- Mean change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT-F) scores(First day of treatment Cycle1, Cycle 2, Cycle 6 (each cycle is 28 days in length) and at end-of-treatment visit (up to approximately 4 years).)
- Adverse events by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5(From Day 1 until end of treatment visit (up to approximately 4 years).)
- PFS by investigator assessment according to RECIST version 1.1.(From randomization date to date of first documentation of progression OR death (up to approximately 4 years).)
- Objective response rate (ORR)(Screening, Cycle 3 Day 1 (C3D1), Cycle 5 Day 1 (C5D1), Cycle 7 Day 1 (C7D1), and on Day 1 of every third cycle (each cycle is 28 days in length) thereafter until end-of-treatment visit (up to approximately 4 years).)
- Duration of response (DOR)(Screening, Cycle 3 Day 1 (C3D1), C5D1, C7D1, and on Day 1 of every third cycle (each cycle is 28 days in length) thereafter until end-of-treatment visit (up to approximately 4 years).)
- DOR by RECIST version 1.1 in cross-over patient population(Screening, Cycle 3 Day 1 (C3D1), C5D1, C7D1, and on Day 1 of every third cycle (each cycle is 28 days in length) thereafter until end-of-treatment visit (up to approximately 4 years).)
- ORR by RECIST version 1.1 in cross-over patient population(Screening, Cycle 3 Day 1 (C3D1), C5D1, C7D1, and on Day 1 of every third cycle (each cycle is 28 days in length) thereafter until end-of-treatment visit (up to approximately 4 years).)