2023-506229-12-00已完成2 期
A phase II, randomized, open-label study to assess the efficacy, safety, and pharmacokinetics (PK) of maintenance cabozantinib (XL184) plus best supportive care (BSC) versus BSC in children, adolescents and young adults (AYA) with unresectable residual osteosarcoma either at diagnosis or at first relapse after standard treatment.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 53
- 主要终点
- Progression-free Survival (PFS) assessed by Blinded Independent Radiology Committee (BIRC) PFS defined as the time from the date of randomization to the date of first documented disease progression or the date of death due to any cause, whichever occurs first. Time Frame: From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months)
研究概览
简要总结
To assess the efficacy of maintenance cabozantinib plus BSC versus BSC in improving the PFS in participants with osteosarcoma
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •Participants must be ≥5 and ≤30 years of age at the time of study entry.
- •Adequate organ and marrow function.
- •Adequately controlled blood pressure (BP) with or without antihypertensive medications
- •Male and/or female (according to their reproductive organs and functions assigned by chromosomal complement). (FDA 2016)
- •Contraception and barriers as well as pregnancy testing is required as appropriate for the age and sexual activity of pediatric participants and as required by local regulations.
- •All participants (typically ≥18 years) and/or their parents or legal guardians must sign a written informed consent and assent must be obtained from minor participants according to local guidelines.
- •Histologically or cytologically confirmed diagnosis of high-grade osteosarcoma as defined by a local pathologist
- •Participants with unresectable residual disease after standard chemotherapy treatment at diagnosis or first relapse (treated with systemic chemotherapy). A minimum of 4 cycles of systemic chemotherapy (or minimum of 2 cycles if chemotherapy was stopped early due to toxicity) must have been received
- •Measurable residual or evaluable disease by RECIST version 1.
- •Participants will be considered with evaluable disease if they have only non-measurable disease as per RECIST version 1.1 criteria.
- •Absence of PD (defined by the investigator according to RECIST version 1.1) at study entry. Note, the two most recent radiological evaluations (e.g. computerised tomography (CT) or magnetic resonance imaging (MRI) scan) including the one following completion of chemotherapy should be available later to facilitate BIRC review.
- •Chemotherapy must be the last anticancer treatment received by participants before study entry and must have been completed at least 4 weeks but no longer than 2 months before randomization.
- •Participants must have recovered to Grade ≤1, except for alopecia, ototoxicity, and Grade ≤2 peripheral neuropathy, per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) from the acute toxic effects of all prior anticancer therapy at study entry, unless AEs are clinically nonsignificant and/or stable on supportive therapy, per investigator clinical judgment.
- •Life expectancy >6 months.
- •Performance level: participants must have a Lansky or Karnofsky performance status score of ≥70 corresponding to ECOG categories 0-1.
排除标准
- •Low grade osteosarcoma and periosteal osteosarcoma
- •Any other active malignancy at time of first dose of study intervention or diagnosis of another malignancy within 3 years prior to first dose of study intervention that requires active treatment.
- •Pregnancy or breast-feeding.
- •Participants who in the opinion of the investigator may not be able to comply with the requirements of the study are not eligible
- •Major surgery (eg, orthopaedic surgery, removal or biopsy of brain metastasis) within 8 weeks before randomization. Complete wound healing from major surgery must have occurred 4 weeks before randomization and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before randomization. Participants with clinically relevant ongoing complications from prior surgery are not eligible.
- •Previous treatment with cabozantinib or another MET/hepatocyte growth factor (HGF) inhibitor (e.g., tivantinib, crizotinib).
- •Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer, before first dose of study intervention.
- •Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study intervention (or washout of at least 5 half-lives, whichever is shorter).
- •Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 4 weeks prior to randomization.
- •Participants who have an uncontrolled/active infection requiring systemic therapy.
- •Participants who are unable to swallow intact tablets.
- •Participants with uncontrolled, significant intercurrent or recent illness.
- •Previously identified allergy or hypersensitivity to components of the study treatment formulations.
研究组 & 干预措施
CABOMETYX 20 mg film-coated tablets, CABOMETYX 60 mg film-coated tablets
Test
干预措施: CABOMETYX 20 mg film-coated tablets (Drug)
CABOMETYX 20 mg film-coated tablets, CABOMETYX 60 mg film-coated tablets
Test
干预措施: CABOMETYX 60 mg film-coated tablets (Drug)
结局指标
主要结局
Progression-free Survival (PFS) assessed by Blinded Independent Radiology Committee (BIRC) PFS defined as the time from the date of randomization to the date of first documented disease progression or the date of death due to any cause, whichever occurs first. Time Frame: From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months)
Progression-free Survival (PFS) assessed by Blinded Independent Radiology Committee (BIRC) PFS defined as the time from the date of randomization to the date of first documented disease progression or the date of death due to any cause, whichever occurs first. Time Frame: From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months)
次要结局
- Progression-free survival (PFS) rate assessed by BIRC: PFS rate at 4 months and 1 year was defined as the probability that participants have not progressed by BIRC assessment and remain alive at 4 months and 1 year. Time Frame: 4 months and 1 year after randomization
- Objective response rate (ORR) assessed by BIRC: ORR defined as the proportion of participants who have achieved complete response (CR) or partial response (PR) determined by BIRC. Time Frame: Approximately 34 months after randomization
- Disease control rate (DCR) assessed by BIRC: Defined as the proportion of participants who have achieved CR, PR, or stable disease (SD) determined by BIRC. Time Frame: Approximately 34 months after randomization
- Overall survival (OS): Defined as the probability participants alive at 1 year. Time Frame: At 1 year after randomization
- PFS assessed by investigator: Defined as the time from the date of randomization to the date of first documented disease progression determined by investigator or the date of death due to any cause, whichever occurs first. Time Frame: From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months)
- PFS rate assessed by investigator: Defined as the probability that participants have not progressed by investigator assessment and remain alive at 4 months and 1 year.Time Frame: At 4 months and 1 year after randomization
- ORR assessed by investigator: Defined as the proportion of participants who have achieved complete response (CR) or partial response (PR) determined by investigator using RECIST version 1.1. Time Frame: Approximately 34 months after randomization
- DCR assessed by investigator Defined as the proportion of participants who have achieved CR, PR, or SD determined by investigator. Time Frame: Approximately 34 months after randomization
- Overall survival (OS): Defined as the time from date of randomization to the date of death, from any cause. Time Frame: From randomization until death or last contact (approximately 34 months)
- Percentage of participants with Treatment Emergent Adverse Event (TEAEs) and Adverse Events of Special Interest (AESIs). [Time Frame: From screening till 30 days after last dose for AE, and until resolution or stabilization for treatment related SAE]
- Area Under Curve (AUC) at steady state. Time Frame: At Cycle 1 Day 1 and Cycle 2 Day 1
- Average concentration (Cavg) at steady state. Time Frame: Time Frame: At Cycle 1 Day 1 and Cycle 2 Day 1
- Minimum concentration (Cmin) at steady state. Time Frame: Time Frame: At Cycle 1 Day 1 and Cycle 2 Day 1
- Maximal concentration (Cmax) at steady state. Time Frame: Time Frame: At Cycle 1 Day 1 and Cycle 2 Day 1
- Acceptability and palatability in children and adolescents assessed using a horizontal visual assessment scale. Five-point facial hedonic scale with a correlated 100-point horizontal visual analog scale (FHS/VAS-5) will be used to assess acceptability and palatability in children and adolescents. Time Frame: Day of first dose
- . Change from baseline in score for all Paediatric QoL Inventory (PedsQL) Scales including Generic Core Scales and Cancer Modules. [Time Frame: From screening to 30 days after last dose]
- Change from baseline in EORTC QLQ-C30 for adult participants. [Time Frame: From screening to 30 days after last dose]
研究者
Senior Vice President, GRA and R&D Quality
Scientific
Ipsen Innovation
研究点 (53)
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