A Phase 2 Non-Comparative Randomized Open-Label Study of Multiple Regimens of Single-Agent XL184 in Subjects With Grade IV Astrocytic Tumors in First or Second Relapse
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Exelixis
- 入组人数
- 19
- 试验地点
- 19
- 主要终点
- Randomized Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
This study was conducted in subjects with grade IV astrocytic tumors (a type of cancer that can occur in the brain or spinal cord) in first or second relapse.
详细描述
The goal of this clinical trial is to learn if the drug cabozantinib works for people with astrocytic tumors. It also was designed to learn about the safety of cabozantinib. The main questions are:
- Does cabozantinib work and how well do patients tolerate the drug for over 12 weeks.
- Was the drug safe and how well could patients tolerate treatment for the entire treatment period.
Participants were assigned to one of the four treatment groups:
Arm 1. Take cabozantinib at a dose of 25 mg once every day (po QD) continuously until progression.
Arm 2. Take cabozantinib at a dose of 75 mg once every day continuously until progression.
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
- •The subject has histologically confirmed diagnosis at any time of grade IV astrocytic tumor as determined by the investigator. Tumor samples will be required for pathology review.
- •The subject has received prior standard radiation for any grade astrocytic tumor.
- •The subject has received prior temozolomide (Temodar) therapy
- •The subject has had one or two progressions as grade IV astrocytic tumor from any grade, as determined by investigator
- •The subject must have a qualifying brain MRI scan within a specific timeframe prior to start of study treatment
- •For subjects with recent tumor resection or biopsy, starting on study must occur a specified amount of time after the surgery and the subject must have recovered from the effects of surgery
- •The subject has a Karnofsky Performance Status ≥ 70% and has the ability to swallow whole capsules
- •The subject is capable of understanding the informed consent and has signed the informed consent document
- •The subject has adequate organ and marrow function
- •Sexually active subjects (male and female) must agree to use medically accepted methods of contraception during the course of the study and for 6 months following discontinuation of study treatment
- •The subject has had no other diagnosis of malignancy (certain exceptions apply)
- •Female subjects of childbearing potential must have a negative pregnancy test at screening
排除标准
- •The subject has received certain prior anticancer therapies within a certain amount of time before starting study treatment
- •The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin
- •The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or CT scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible
- •The subject is unable to undergo MRI scan (eg, has pacemaker)
- •The subject has received enzyme-inducing anti-epileptic agents within a certain time prior to starting study treatment (eg, carbamazepine, phenytoin, phenobarbital, primidone)
- •The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade ≤ 1 from AEs (except alopecia and lymphopenia) due to surgery, or other medications that were administered prior to study start
- •The subject has evidence of unhealed wounds
- •The subject is pregnant or breast-feeding
- •The subject has serious intercurrent illness or a recent history of serious disease
- •The subject has inherited bleeding diathesis or coagulopathy (disease affecting how blood clots) with the risk of bleeding
- •The subject has a history of any medical or surgical conditions (eg, stomach or intestinal surgery or resection) that would potentially interfere with or alter gastrointestinal function
- •The subject has a history of idiopathic pulmonary fibrosis or interstitial lung disease
- •The subject has received any live virus vaccine or any inactivated vaccine within a certain amount of time before starting study treatment
研究组 & 干预措施
Arm 2 - cabozantinib, 75 mg
Starting dose of 75 mg, po QD, continuously
干预措施: Cabozantinib (Drug)
Arm 4 - cabozantinib, 125 mg
Initially, the starting dose was 125 mg, po QD for 2 weeks, followed by 1 week off.
For the remainder of the treatment, the dosing frequency was reduced to 125 mg, po QD every 3 weeks, followed by 1 week of rest for the remainder of the treatment period.
干预措施: Cabozantinib (Drug)
Arm 3 - cabozantinib, 125 mg followed by 50 mg
Starting dose of 125 mg, po QD for 2 weeks, followed by 50 mg, po QD for the remainder of the treatment period.
干预措施: Cabozantinib (Drug)
Arm 1 - cabozantinib, 25 mg
Starting dose of 25 mg, once a day by mouth (po QD) continuously
干预措施: Cabozantinib (Drug)
结局指标
主要结局
Randomized Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to 13 months
An AE was defined as any event with an onset date on or after the date of first dose of study drug, or any ongoing event on the date of first dose that worsened in severity after the date of first dose. TEAEs were defined as AEs that started on or after the first administration of study drug up to the date of last dose plus 30 days. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
Expansion Phase: Objective Response Rate (ORR)
时间窗: Up to 13 months
ORR was defined as the number of participants for whom the best overall response at the time of data cutoff is confirmed complete response (CR) or confirmed partial response (PR) as assessed per modified Response Assessment in Neuro-Oncology (RANO) criteria. CR = Disappearance of all enhancing target lesion(s) and no glucocorticoids (other than a physiologic replacement dose of a maximum of 1.2 mg dexamethasone equivalent dose per day) taken for the 5 days immediately preceding the date of the current magnetic resonance imaging (MRI). PR = ≥50% decrease in the sum of the products of perpendicular diameters of all target enhancing lesions on the current MRI scan compared to the baseline MRI scan and glucocorticoids stable or decreased. The sponsor terminated the study early due to business reasons before entering the expansion phase. As such, no data were collected for efficacy analyses.
次要结局
- Expansion Phase: Progression Free Survival at 6 Months as Per Independent Radiology Facility(Month 6)