A Multicenter, Randomized, Open-label, Phase 3 Trial Comparing Selpercatinib to Physicians Choice of Cabozantinib or Vandetanib in Patients With Progressive, Advanced, Kinase Inhibitor Naïve, RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 291
- 试验地点
- 141
- 主要终点
- Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
研究概览
简要总结
The reason for this study is to see if the study drug selpercatinib is safe and more effective compared to a standard treatment in participants with rearranged during transfection (RET)-mutant medullary thyroid cancer (MTC) that cannot be removed by surgery or has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.
详细描述
Adaptive sample size re-estimation will be performed at interim analysis. The sample size could be increased from approximately 250 to 400 depending on the results of interim analysis.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •An additional validated oncogenic driver in MTC if known that could cause resistance to selpercatinib treatment. Examples include, but are not limited to RAS or BRAF gene mutations and NTRK gene fusions.
- •Symptomatic central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression.
- •Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months, history of Torsades de pointes, or prolongation of the QTcF >470 milliseconds on more than one electrocardiogram (ECG) during screening. Participants who are intended to receive vandetanib if randomized to the control arm are ineligible if QTcF is >450 milliseconds.
- •Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing uncontrolled intercurrent illness.
- •Active hemorrhage or at significant risk for hemorrhage.
- •Other malignancy unless nonmelanoma skin cancer, carcinoma in situ or malignancy diagnosed ≥2 years previously and not currently active. Participants with multiple endocrine neoplasia type 2 (MEN2) associated pheochromocytoma may be eligible.
研究组 & 干预措施
Selpercatinib - Treatment A (TRT A)
160 milligrams Selpercatinib administered orally (PO) twice daily (BID).
Adolescent Dose: 92 milligrams per square meter (mg/m2) BID (not to exceed 160 mg BID).
干预措施: Selpercatinib (Drug)
Cabozantinib or Vandetanib - Treatment B (TRT B)
140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice.
Cabozantinib Adolescent Dose: 40 mg/m2.
Vandetanib Adolescent Dose:
- 0.7 - <0.9 - 100 mg every other day (QOD)
- 0.9 - <1.2 - 100 mg QD
- 1.2 - <1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg
- ≥1.6 - 200 QD
干预措施: Cabozantinib (Drug)
Cabozantinib or Vandetanib - Treatment B (TRT B)
140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice.
Cabozantinib Adolescent Dose: 40 mg/m2.
Vandetanib Adolescent Dose:
- 0.7 - <0.9 - 100 mg every other day (QOD)
- 0.9 - <1.2 - 100 mg QD
- 1.2 - <1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg
- ≥1.6 - 200 QD
干预措施: Vandetanib (Drug)
结局指标
主要结局
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR)
时间窗: Baseline to Progressive Disease or Death from Any Cause, Whichever Occurs First, Up to 39 Months
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria, or death from any cause in the absence of BICR-documented progressive disease. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
次要结局
- Treatment Failure-Free Survival (TFFS) by Blinded Independent Committee Review (BICR)(Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months)
- Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR(Baseline through Disease Progression or Death Up to 39 Months)
- Duration of Response (DoR) by BICR(Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 39 Months)
- Overall Survival (OS)(Baseline)
- PFS2 by Investigator(Baseline)
- Comparative Tolerability: Number of Weeks With High Side Effect Bother Based Score of 3 or 4 on the Functional Assessment of Cancer Therapy Item GP5 (FACT-GP5)(Baseline to Progressive Disease, Unacceptable Toxicity or Death from Any Cause Up to 39 Months)
- The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants With RET-Positive Specimens as Called by the Central Lab, Which is Also RET-Positive as Called by a Local Lab (Positive Percent Agreement)(Baseline)