NCT06997588招募中2 期
Study Assessing the Efficacy, Safety and Pharmacokinetics of Alpelisib in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 104
- 试验地点
- 41
- 主要终点
- Proportion of participants with a confirmed objective response by BIRC
研究概览
简要总结
This study is designed to demonstrate the efficacy and assess safety and tolerability of oral daily alpelisib in participants with PIK3CA-related overgrowth spectrum (PROS).
详细描述
The study consists of a screening period of up to 42 days, a core period of 48 weeks and an extension period of up to 2 years to assess the efficacy, safety and pharmacokinetic (PK) of alpelisib in pediatric and adult participants with PROS.
Screening Period: Potential participants will be assessed for eligibility and undergo a whole body MRI scan to evaluate PROS-related lesions. Only those who meet all inclusion criteria will be eligible for randomization.
Core Period: Baseline is defined as the last available evaluation prior to the first dose of study treatment. Participants in Group 1 and Group 2 will be enrolled and treated with alpelisib in an open-label fashion.
- Group 1 (adults): will start with 250 mg once daily, with no dose escalation allowed.
- Group 2 (children and adolescents): will start with 50 mg once daily for participants aged 2 to <6 years, and 125 mg once daily for participants aged 6 to <18 years.
Extension 1 Period: Participants in both groups will continue their treatment under the same rules as the core period. This period will last until Week 168 following the completion of the core period for each participant. Those who complete this period before the end of the study will transition to the Extension 2 period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged ≥2 years at the time of informed consent/assent.
- •Participants with diagnosis of PROS (according to Clinical Diagnostic Criteria for PROS proposed by Keppler Noreuil et al 2014) with symptomatic AND progressive overgrowth, who have syndromic disease or isolated features (with the exception of isolated macrodactyly, macrocephaly or epidermal nevus) at the time of informed consent/assent.
- •Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local laboratories using a DNA-based test AND available archival tissue (if archival tissue sample is not available, a fresh biopsy should be performed, if it is not clinically contraindicated) at the time of informed consent/assent.
- •Karnofsky (in participants >16 years of age at study entry) or Lansky (≤16 years of age at study entry) performance status index ≥
- •PGI-S score of mild, moderate, severe, or very severe at screening.
- •Adequate bone marrow and organ function.
- •Presence of at least 1 PROS-related measurable lesion (longest diameter ≥2 cm) confirmed by BIRC assessment and associated with complaints, clinical symptoms or functional limitations affecting the participant's everyday life.
排除标准
- •Participant with only isolated macrodactyly, epidermal nevus/nevi and macroencephaly (the only clinical feature or a combination of any of three of them), in absence of other PROS-related lesions at the time of informed consent/assent.
- •Previous treatment with alpelisib and/or any other phosphatidylinositol 3-kinase (PI3K) inhibitor(s) (except treatment attempt, defined as the attempt to treat PROS with any of PI3K inhibitors, with treatment duration less than 2 weeks and stopped at least 4 weeks prior to the first dose of study medication with alpelisib).
- •Debulking or other major surgery performed within 3 months at the time of informed consent/assent.
- •Radiation exposure for PROS treatment purpose within 12 months prior to informed consent/assent.
- •Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per CTCAE v4.03) within 30 days before informed consent/assent, and/or sclerotherapy/embolization for vascular complications performed within 6 weeks before informed consent/assent.
- •Clinically meaningful bleeding from PROS-related lesion (Grade 2 and more as per CTCAE v4.03) within 30 days before study treatment initiation.
- •Participants with clinically significant worsening of PROS-related laboratory abnormalities, physical signs and symptoms (such as, but not limited to increase of D-dimers, worsening of underlying pain, newly occurring swelling or redness) indicating an uncontrolled condition during the screening phase.
- •Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Group 1
Experimental
Adult participants ≥18 years of age.
干预措施: Alpelisib (Drug)
Group 2
Experimental
Children and adolescents 2 to <18 years of age.
干预措施: Alpelisib (Drug)
结局指标
主要结局
Proportion of participants with a confirmed objective response by BIRC
时间窗: Up to Week 48
Confirmed objective response is defined as achieving radiological response, confirmed by a subsequent assessment performed at least after 4 weeks. The achievement of radiological response requires ≥20% reduction from baseline in the sum of target lesion volumes (1 to 3 target lesions, assessed by Magnetic Resonance Imaging (MRI) by a blinded independent review committee (BIRC)), provided that none of the individual target lesions has ≥20% increase from nadir, and in absence of progression of non-target lesions and without new lesions.
次要结局
- Change from baseline (as assessed by BIRC) in target lesion volume(Baseline, Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168))
- Change from baseline (as assessed by BIRC) in MRI-measurable non-target lesion volume(Baseline, Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168))
- Change from baseline (as assessed by BIRC) in all MRI-measurable (target and non-target) lesion volume(Baseline, Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168))
- Change from baseline (as assessed by BIRC) in other non-target lesion(Baseline, Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168))
- Appearance of new lesions (as assessed by BIRC)(Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168))
- Proportion of participants with a radiological response(Week 12, Week 24, Week 48, Week 96, Week 144, Week 168, End of Treatment (last dose +< 14 day - Only for participants discontinuing on or prior to week 168))
- Duration of Response (DoR)(From first documented response until progression of PROS lesions or death, assessed up to approximately 3 years)
- Alpelisib plasma concentration(Week 1 Day 1 (Post-dose 3 hour), Week 4 Day 1 (Pre-dose and Post-dose 3 hour), Week 12 Day 1 (Pre-dose and Post-dose 3 hour))
- Change from Baseline in Brief Pain Inventory (BPI)(Baseline, Week 4, Week 8, Week 12, Week 16, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, End of Treatment (last dose +< 14 days))
- Change from Baseline in Wong-Baker Faces Scale(Baseline, Week 4, Week 8, Week 12, Week 16, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, End of Treatment (last dose +< 14 days))
- Change from Baseline in Patient Global Impression of Symptom Severity (PGI-S)(Baseline, Week 4, Week 8, Week 12, Week 16, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, End of Treatment (last dose +< 14 days))
- Time to Treatment Failure (TTF)(From Baseline up to approximately 3 years)
- Overall Clinical Response(From Baseline up to approximately 3 years)
- Change from Baseline in symptoms and complications/comorbidities associated with PROS(From Baseline up to approximately 3 years)
- Percentage of participants with healthcare visits/hospitalized due to PROS(Up to at least 3 years)
- Percentage of participants with surgeries required to manage PROS(Up to at least 3 years)
- Number of Adverse Events and Serious Adverse Events as assessed by CTCAE criteria(Up to at least 3 years)
研究者
研究点 (41)
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