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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT05948943
Registration number
NCT05948943
Ethics application status
Date submitted
4/07/2023
Date registered
17/07/2023
Titles & IDs
Public title
Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.
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Scientific title
A Two-stage Double-blind, Randomized, Placebo-controlled Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.
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Secondary ID [1]
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2023-504146-60-00
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Secondary ID [2]
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CBYL719P12201
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Universal Trial Number (UTN)
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Trial acronym
EPIK-L1
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Lymphatic Malformations
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Condition category
Condition code
Cardiovascular
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Diseases of the vasculature and circulation including the lymphatic system
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Reproductive Health and Childbirth
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Fetal medicine and complications of pregnancy
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Alpelisib
Treatment: Drugs - Placebo
Experimental: Adult participants, alpelisib dose 1 (Stage 1) - Adult participants (=18 years of age) who will receive dose 1 of alpelisib an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1)
Experimental: Adult participants, alpelisib dose 2 (Stage 1) - Adult participants (=18 years of age) who will receive dose 2 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1).
Experimental: Pediatric participants (6-17 years of age), alpelisib dose 2 (Stage 1) - Pediatric participants 6-17 years of age who will receive dose 2 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1)
Experimental: Pediatric participants (6-17 years of age), alpelisib dose 3 (Stage 1) - Pediatric participants 6-17 years of age who will receive dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier (Stage 1).
Experimental: Adult participants, alpelisib (Stage 2) - Adult participants (=18 years of age) who will receive alpelisib at the dose selected for confirmatory phase in adult participants (Stage 2)
Placebo comparator: Adult participants, placebo (Stage 2) - Adult participants (=18 years of age) who will receive matching placebo
Experimental: Pediatric participants (6-17 years of age), alpelisib (Stage 2) - Pediatric participants (6-17 years of age) who will receive alpelisib at the dose selected for confirmatory phase in pediatric participants (Stage 2)
Placebo comparator: Pediatric participants (6-17 years of age), placebo (Stage 2) - Pediatric participants (6-17 years of age) who will receive matching placebo
Experimental: Pediatric participants (2-5 years of age), alpelisib (Stage 2) - Pediatric participants of 2-5 years who will dose 3 of alpelisib in an open-label fashion for at least 24 weeks unless they discontinue earlier
Treatment: Drugs: Alpelisib
In Stage 1: adult participants (=18 years of age) will receive dose 1 or dose 2 of alpelisib; pediatric participants (6-17 years of age) will recieve dose 2 or dose 3 of alpelisib.
In Stage 2: Adult participants will receive alpelisib at the dose selected for confirmatory phase in adult participants; pediatric participants (6-17 years of age) will will receive alpelisib at the dose selected for confirmatory phase in pediatric participants; and pediatric participants of 2-5 years of age will receive dose 3 of alpelisib
Treatment: Drugs: Placebo
In Stage 2, participants will receive matching placebo for 24 weeks of the study
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Stage 2:Radiological response rate at Week 24 of Stage 2 (adult and pediatric (6 - 17 years of age) participants)
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Assessment method [1]
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Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions. The percentage of participants with a radiological response at Week 24 of Stage 2 in adult and pediatric (6-17 years of age) groups will be assessed
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Timepoint [1]
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Baseline, Week 24
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Secondary outcome [1]
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Stage 2: Percentage of participants with at least a 1-point improvement compared to baseline based on patient global impression of severity (PGI-S) scale at Week 24 of Stage 2 (adult and pediatric (6 - 17 years of age) participants)
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Assessment method [1]
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PGI-S is a single item measure to assess the overall severity of a patient's condition. This single item instrument uses a 5-point rating scale, which ranges from 1 (no symptoms) to 5 (very severe). Lower scores indicate better health status. The percentage of participants with at least a 1-point improvement compared to baseline at Week 24 of Stage 2 in adult and pediatric (6-17 years of age) groups will be assessed
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Timepoint [1]
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Baseline, Week 24
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Secondary outcome [2]
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Stage 2: Percentage of participants with a radiological response at Week 24 of Stage 2 (pediatric participants 2-5 years of age)
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Assessment method [2]
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Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions. The percentage of participants with a radiological response at Week 24 of Stage 2 in pediatric participants 2-5 years of age will be assessed
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Timepoint [2]
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Baseline, Week 24
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Secondary outcome [3]
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Stage 2: Change from baseline in patient global impression of change (PGI-C) scale (adult and pediatric (6-17 years of age) participants)
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Assessment method [3]
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PGI-C is a single item measure to assess the change in overall symptoms severity since the start of study. This single item instrument uses a 7-point rating scale, which ranges from 1 (very much improved) to 7 (very much worse). Lower scores indicate better health status. The change from baseline in PGI-C score will be assessed in adult and pediatric (6-17 years of age) participants
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Timepoint [3]
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Up to approximately 8 years
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Secondary outcome [4]
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Stage 2: Change from baseline in patient-reported outcomes measurement information system (PROMIS) profile domains(adult and pediatric (6-17 years of age) participants)
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Assessment method [4]
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The PROMIS-29 plus 2 Profile v2.1 (completed by adult participant) includes 29 items across domains of depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, ability to participant in social roles and activities, cognitive function abilities and pain intensity..
The PROMIS Pediatric-25 Profile v2.0 (completed by children over 8 years of age) and PROMIS Parent-Proxy-25 Profile v2.0 (completed by parents for children under 8 years of age) include 25 items across the domains of depressive symptoms, anxiety, physical function-mobility, pain interference, fatigue, and peer relationships and pain intensity All items (except the pain intensity item) use a 5-point Likert scale, which ranges from 1 (not at all) to 5 (very much). The pain internsity item is scored on a 0-10 numeric rating scale, where 0 represents "no pain" and 10 represents "worst imaginable pain".
The change from baseline in PROMIS domains will be assessed
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Timepoint [4]
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Up to approximately 8 years
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Secondary outcome [5]
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Stage 2: Change from baseline in investigator global impression of change (IGIC) scale (adult and pediatric (6-17 years of age) participants)
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Assessment method [5]
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The IGIC involves a single question that asks the investigator to rate the change in the patient's condition since the start of treatment or intervention, using a 7-point scale ranging from 1 (Very much improved) to 7 (Very much worse). The change from baseline in IGIC score will be assessed in adult and pediatric (6-17 years of age) participants
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Timepoint [5]
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Up to approximately 8 years
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Secondary outcome [6]
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Stage 2: Change from baseline in health utilities of the EuroQol 5-dimension (EQ-5D) (adult and pediatric (6-17 years of age) participants)
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Assessment method [6]
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The EQ-5D-5L (completed by adult participants) includes 5 items addressing dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 5 response options, ranging from 1=no problems to 5=extreme problems The EQ-5D-Y (completed by children over 8 years of age) and EQ-5D-Y Proxy version (completed by parent for participants under 8 years of age or unable to record for themselves) includes 5 items addressing dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 3 response options, ranging from 1= no problems to 3= a lot of problems
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Timepoint [6]
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Up to approximately 8 years
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Secondary outcome [7]
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Duration of response (DOR) in adult and pediatric participants who receive alpelisib (Stage 1 and 2)
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Assessment method [7]
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DOR is defined as the time from first documented response until progression of LyM lesions by BIRC or death. This analysis only applies to participants who are on treatment with alpelisib (Stage 1 and 2) and who achieve response.
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Timepoint [7]
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Up to approximately 8 years
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Secondary outcome [8]
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Radiological response rate of alpelisib in adult and pediatric (6-17 years of age) participants (Stage 1)
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Assessment method [8]
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Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC at Week 24, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.
The percentage of participants (adult and pediatric 6-17 years of age) with radiological response at Week 24 of Stage 1 will be assessed.
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Timepoint [8]
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Baseline, Week 24
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Secondary outcome [9]
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Radiological response rate of alpelisib in adult and pediatric participants (Stage 1 and 2)
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Assessment method [9]
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Radiological response defined by achieving at least 20% reduction in the sum of target lesion volumes (1 to 3 lesions), assessed by MRI by a BIRC, provided that none of the individual target lesions has at least 20% increase from baseline and in absence of progression of non-target lesions and without new lesions.
The percentage of participants who receive alpelisib (Stage 1 and 2) with radiological response will be assessed.
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Timepoint [9]
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Up to approximately 8 years
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Secondary outcome [10]
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Alpelisib plasma concentrations (Stage 1 and 2)
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Assessment method [10]
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Alpelisib plasma concentrations in adult and pediatric participants (Stage 1 and 2).
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Timepoint [10]
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On Day 1 of Week 8, 16, 24, 48 and 120
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Secondary outcome [11]
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Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants at Week 24 (Stage 1 and 2)
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Assessment method [11]
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Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants at Week 24 (Stage 1 and 2)
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Timepoint [11]
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Week 24
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Secondary outcome [12]
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Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants (Stage 1 and 2)
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Assessment method [12]
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Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants (Stage 1 and 2)
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Timepoint [12]
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Up to approximately 8 years
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Secondary outcome [13]
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Change from baseline in LyM lesions in adult and pediatric participants at Week 24 (Stage 1 and 2)
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Assessment method [13]
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Change from baseline in the sum of target lesion volumes, the sum of MRI-measurable non-target lesion (if applicable) volumes, and the sum of all MRI-measurable lesion (target and non-target) volumes as assessed by BIRC at Week 24 in adult and pediatric participants (Stage 1 and 2)
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Timepoint [13]
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Baseline, Week 24
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Secondary outcome [14]
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Change from baseline in LyM lesions in adult and pediatric participants (Stage 1 and 2)
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Assessment method [14]
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Change from baseline in the sum of target lesion volumes, the sum of MRI-measurable non-target lesion (if applicable) volumes, and the sum of all MRI-measurable lesion (target and non-target) volumes as assessed by BIRC in adult and pediatric participants (Stage 1 and 2)
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Timepoint [14]
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Up to approximately 8 years
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Secondary outcome [15]
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Percentage of participants with changes in non-target lesions in adult and pediatric participants at Week 24 (Stage 1 and 2)
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Assessment method [15]
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Percentage of participants with changes in non-target lesions as assessed by BIRC at Week 24 in adult and pediatric participants (Stage 1 and 2)
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Timepoint [15]
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Baseline, Week 24
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Secondary outcome [16]
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Percentage of participants with changes in non-target lesions in adult and pediatric participants (Stage 1 and 2)
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Assessment method [16]
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Percentage of participants with changes in non-target lesions as assessed by BIRC in adult and pediatric participants (Stage 1 and 2)
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Timepoint [16]
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Up to approximately 8 years
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Secondary outcome [17]
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Percentage of participants with new lesions in adult and pediatric participants at Week 24 (Stage 1 and 2)
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Assessment method [17]
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The percentage of participants with new lesions as assessed by BIRC at Week 24 in adult and pediatric participants (Stage 1 and 2)
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Timepoint [17]
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Baseline, Week 24
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Secondary outcome [18]
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Percentage of participants with new lesions in adult and pediatric participants (Stage 1 and 2)
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Assessment method [18]
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The percentage of participants with new lesions as assessed by BIRC in adult and pediatric participants (Stage 1 and 2)
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Timepoint [18]
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Up to approximately 8 years
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Eligibility
Key inclusion criteria
Key
* Participant must be willing to remain at the clinical site as required by the protocol and be willing to adhere to study restrictions and examination schedules.
* Participant has a physician confirmed and documented diagnosis of a LyM at the time of informed consent
* Participant is not considered as a candidate for or is not willing to receive local therapy options including but not limited to sclerotherapy, embolization, and surgery until the completion of Week 24 in Stage 1 and 2.
* Participant has evidence of a somatic mutation(s) in the PIK3CA gene
* Participant has at least one measurable LyM lesion confirmed by BIRC assessment prior to randomization.
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Minimum age
2
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Participant has a physician-confirmed and documented diagnosis of PROS at the time of informed consent.
* Participant has a physician-confirmed and documented diagnosis of a Central Conducting Lymphatic Anomaly, General Lymphatic Anomaly, Gorham-Stout disease, Kaposiform lymphangiomatosis at the time of informed consent.
* Participant has a known history of Stevens-Johnson syndrome, erythema multiforme, or toxic epidermal necrolysis at the time of informed consent.
* Participant has an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at the time of informed consent.
* Participant had previous treatment with alpelisib and/or any other PI3K inhibitors with treatment duration longer than 2 weeks at the time of informed consent.
Other inclusion/exclusion criteria may apply
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
24/11/2023
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
28/11/2031
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Actual
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Sample size
Target
230
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
QLD
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Recruitment hospital [1]
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Novartis Investigative Site - Brisbane
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Recruitment postcode(s) [1]
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4101 - Brisbane
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
0
0
United States of America
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State/province [2]
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0
Missouri
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Country [3]
0
0
United States of America
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State/province [3]
0
0
Pennsylvania
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Country [4]
0
0
United States of America
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State/province [4]
0
0
Texas
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Country [5]
0
0
United States of America
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State/province [5]
0
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Washington
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Country [6]
0
0
Belgium
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State/province [6]
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Bruxelles
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Country [7]
0
0
France
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State/province [7]
0
0
Bordeaux Cedex
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Country [8]
0
0
France
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State/province [8]
0
0
Bron Cedex
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Country [9]
0
0
France
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State/province [9]
0
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Caen
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Country [10]
0
0
France
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State/province [10]
0
0
Lille
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Country [11]
0
0
France
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State/province [11]
0
0
Marseille
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Country [12]
0
0
France
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State/province [12]
0
0
Montpellier
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Country [13]
0
0
France
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State/province [13]
0
0
Paris cedex 10
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Country [14]
0
0
France
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State/province [14]
0
0
Tours 9
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Country [15]
0
0
Germany
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State/province [15]
0
0
Baden Wuerttemberg
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Country [16]
0
0
Germany
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State/province [16]
0
0
Freiburg
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Country [17]
0
0
Germany
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State/province [17]
0
0
Koeln
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Country [18]
0
0
Germany
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State/province [18]
0
0
Leipzig
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Country [19]
0
0
Italy
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State/province [19]
0
0
BO
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Country [20]
0
0
Italy
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State/province [20]
0
0
MI
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Country [21]
0
0
Italy
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State/province [21]
0
0
RM
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Country [22]
0
0
Italy
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State/province [22]
0
0
Napoli
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Country [23]
0
0
Spain
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State/province [23]
0
0
Barcelona
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Country [24]
0
0
Spain
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State/province [24]
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0
Madrid
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The main purpose of this study in participants with PIK3CA-mutated lymphatic malformations (LyM) is to assess the change in radiological response and symptom severity upon treatment with alpelisib as compared to placebo.
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Trial website
https://clinicaltrials.gov/study/NCT05948943
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Country
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0
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Phone
0
0
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Fax
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0
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Email
0
0
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Contact person for public queries
Name
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Novartis Pharmaceuticals
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Address
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0
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Country
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0
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Phone
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1-888-669-6682
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Fax
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0
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT05948943