EPIK-P2: A Phase II double-blind study with an upfront, 16-week randomized, placebo-controlled period, to assess the efficacy, safety and pharmacokinetics of alpelisib (BYL719) in pediatric and adult patients with PIK3CA-related overgrowth spectrum (PROS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 164
- 试验地点
- 15
- 主要终点
- Response (yes/no) defined by achieving at least 20% reduction from baseline in the sum of target lesion volumes (1 to 3 lesions, assessed by MRI by a blinded independent review committee (BIRC)), provided that none of the individual target lesions has ≥ 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.
研究概览
简要总结
The primary objective of this study is to demonstrate the efficacy of alpelisib as measured by the proportion of participants randomized to alpelisib with a confirmed objective response by BIRC in at least one of the following groups: • Group 1 (≥ 18 yr-old) • Group 2 (6 - 17 yr-old) The primary scientific question of interest is, for children/adolescents aged 6 to17 years (in Group 2) and adults (Group 1: ≥ 18 years) with PROS, to assess the benefit of alpelisib with regards to the proportion of confirmed responders by BIRC, considering participants that discontinue treatment prior to confirmation of response and participants that receive surgery as rescue therapy for any PROS lesions prior to confirmation of response as non-responders.
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 0-17 Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent and assent (when applicable) from the patient, parent, legal authorized representative or guardian must be obtained prior to any study related screening procedures are performed.
- •Patients with diagnosis of PROS with symptomatic and /or progressive overgrowth and at least one measurable PROS-related lesion confirmed by BIRC assessment.
- •Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local laboratories.
- •A tissue sample (fresh or archival) is to be sent to a Novartis-designated central Laboratory. If archival tissue is not available, collection of a fresh tissue biopsy is required for participants in Groups 1, 2 and 5, if it is not clinically contraindicated. For participants in Groups 3 and 4, a fresh tissue biopsy is not mandatory. For China only: Tissue sample collection and biomarker assessments are not applicable. For Germany only: If archival tissue is available, it must be sent to a Novartis-designated central laboratory. If no archival tissue is available, obtaining a fresh tissue biopsy is recommended, if it is not clinically contraindicated, but is not mandatory.
- •Karnofsky (in patients > 16 years old at study entry)/Lansky (≤16 yrs of age at study entry) performance status index ≥
- •Adequate bone marrow and organ function including Fasting plasma glucose (FPG) ≤ 140 mg/dL (7.7 mmol/L) and Glycosylated hemoglobin (HbA1c) ≤ 6.5% (both criteria have to be met) (as assessed by central laboratory for eligibility).
- •Presence of at least one PROS-related measurable lesion defined as a lesion with longest diameter ≥2 cm, when the volume can be accurately and reproducibly measured by MRI (Magnetic resonance imaging), and associated with complaints, clinical symptoms or functional limitations affecting the patient's everyday life. Measurability must be confirmed by BIRC before randomization.
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.
- •Participants with clinically significant worsening of PROS-related laboratory anomalies, 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, particularly if systemic treatment with any other inhibitor of the PI3K/AKT/mTOR pathway was stopped prior to the start of study treatment. This includes but is not limited to hypercoagulability state in participants not receiving prophylactic treatment.
- •Previous treatment with alpelisib and/or any other 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)
- •Radiation exposure for PROS treatment purpose within the previous 12 months on those PROS areas which are expected to qualify for target lesions (except lesion(s) progressing after completion of radiotherapy) at time of informed consent.
- •Debulking or other major surgery performed within 3 months at time of informed consent.
- •Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per CTCAE v.4.03) within 30 days before informed consent, and/or sclerotherapy/embolization for vascular complications performed within 6 weeks before informed consent. Note: Participants receiving anticoagulants for PROS-related coagulopathy, primary or secondary prophylaxis of thrombosis may be included in the study.
- •Participants in Groups 1, 2 and 5 with documented pneumonitis or interstitial lung disease at time of informed consent and with impaired lung function (e.g., FEV1 or DLCO ≤ 70% of predicted) that is not related to PROS. Participants in Groups 3 and 4 with documented or suspicious pneumonitis or interstitial lung disease based on MRI images at time of informed consent.
- •History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis at time of informed consent.
- •Participants with an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at time of informed consent
- •Known history of seizure, or epilepsy, regardless of relatedness to PROS spectrum at time of informed consent, when epilepsy is not controlled and/or the patient may not be switched to non-enzyme inducing antiepileptic drug(s) at time of informed consent.
研究组 & 干预措施
Placebo to BYL719 50 mg film-coated tablets (Light Yellow) Placebo to BYL719 125 mg film-coated tablets (Dark Yellow)
干预措施: Placebo to BYL719 50 mg film-coated tablets (Light Yellow) Placebo to BYL719 125 mg film-coated tablets (Dark Yellow) (Drug)
BYL719, BYL719, BYL719
干预措施: BYL719 (Drug)
BYL719, BYL719
干预措施: BYL719 (Drug)
结局指标
主要结局
Response (yes/no) defined by achieving at least 20% reduction from baseline in the sum of target lesion volumes (1 to 3 lesions, assessed by MRI by a blinded independent review committee (BIRC)), provided that none of the individual target lesions has ≥ 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.
Response (yes/no) defined by achieving at least 20% reduction from baseline in the sum of target lesion volumes (1 to 3 lesions, assessed by MRI by a blinded independent review committee (BIRC)), provided that none of the individual target lesions has ≥ 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.
次要结局
- The key secondary objective is to demonstrate the efficacy of alpelisib based on the comparison of the proportion of participants achieving response at Week 16 with alpelisib versus placebo in Groups 1 or 2.
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG