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Recruiting NCT05948943

Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.

Phase II / Phase III Interventional Lymphatic Malformations

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Alpelisib, Placebo.
Who it may be relevant to
Registry conditions: Lymphatic Malformations. Basic parameters: 0 years — 100 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Argentina, Australia, Belgium, Czechia +6
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official 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.

Overview

The main purpose of this study in participants with PIK3CA-mutated LyM is to assess the change in radiological response and symptom severity upon treatment with alpelisib film-coated tablets (FCT) as compared to placebo.

Detailed description

This is a phase II/III multi-center study with two stages:

* Stage 1 is designed to select the dose(s) for the confirmatory phase (DSCP) for alpelisib in Stage 2 and will comprise a 24-week open-label core phase in adult (≥18 years of age) and pediatric participants (6-17 years of age) with PIK3CA-mutated LyM, followed by an extension. After eligibility has been confirmed at screening, participants will be randomized in a 1:1 ratio to the different alpelisib doses according to their age. Depending on the results at the end of Stage 1 core phase, the Stage 2 will be opened to adult and/or pediatric participants or the study may be stopped. * Stage 2 is designed to confirm the efficacy and assess safety of alpelisib at the DSCP in participants with PIK3CA-mutated LyM and will comprise a 24-week randomized, double blind, placebo-controlled confirmatory phase in adult (≥18 years of age) and pediatric participants 6-17 years of age followed by an open-label extension. After eligibility has been confirmed at screening participants will be randomized in a 2:1 ratio to alpelisib or placebo.

Additionally, in parallel, Stage 2 will include a 24-week open-label core phase in pediatric participants 0-5 years of age followed by an extension, if pediatric participants will be enrolling in Stage 2.

Based on the results of the 24-week open-label core phase of Stage 1, the dose(s) for Stage 2 will be selected by Novartis in consultation with the Steering Committee (SC). During the 24-week randomized, double blind, placebo-controlled core phase of Stage 2, an Independent Data Monitoring Committee (DMC) will conduct periodic safety and efficacy reviews to assess the risk benefit profile of the treatment.

Interventions

  • Drug 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 receive 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 0-5 years of age will rec
  • Drug Placebo
    In Stage 2, participants will receive matching placebo for 24 weeks of the study

Primary outcome measures

  • Stage 2:Radiological response rate at Week 24 of Stage 2 (adult and pediatric (6 - 17 years of age) participants) [Time frame: Baseline, Week 24]
Secondary outcome measures (12)
  • 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) [Time frame: Baseline, Week 24]
  • Stage 2: Percentage of participants with a radiological response at Week 24 of Stage 2 (pediatric participants 0-5 years of age) [Time frame: Baseline, Week 24]
  • Stage 2: Change from baseline in patient global impression of change (PGI-C) scale (adult and pediatric (6-17 years of age) participants) [Time frame: Up to approximately 8 years]
  • Stage 2: Change from baseline in patient-reported outcomes measurement information system (PROMIS) profile domains(adult and pediatric (6-17 years of age) participants) [Time frame: Up to approximately 8 years]
  • Stage 2: Change from baseline in investigator global impression of change (IGIC) scale (adult and pediatric (6-17 years of age) participants) [Time frame: Up to approximately 8 years]
  • Stage 2: Change from baseline in health utilities of the EuroQol 5-dimension (EQ-5D) (adult and pediatric (6-17 years of age) participants) [Time frame: Up to approximately 8 years]
  • Stage 1 and 2: Duration of response (DOR) in adult and pediatric participants who receive alpelisib [Time frame: Up to approximately 8 years]
  • Stage 1: Radiological response rate of alpelisib in adult and pediatric (6-17 years of age) participants [Time frame: Baseline, Week 24]
  • Stage 1 and 2: Radiological response rate of alpelisib in adult and pediatric participants [Time frame: Up to approximately 8 years]
  • Stage 1 and 2: Alpelisib plasma concentrations [Time frame: On Day 1 of Week 8, 16, 24, 48 and 120]
  • Stage 1 and 2: Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants at Week 24 [Time frame: Week 24]
  • Stage 1 and 2: Percentage of participants with of LyM-related symptoms, complications, and comorbidities on treatment with alpelisib in adult and pediatric participants [Time frame: Up to approximately 8 years]

Eligibility criteria

Inclusion criteria

  • Signed informed consent and assent (when applicable) from the participant, parent, legal authorized representative or guardian.
  • 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 symptomatic LyM at the time of informed consent (Note: the physician must confirm that the LyM cannot be included under the PROS diagnostic criteria).
  • Participant is not considered as a candidate for or is not willing to receive non-drug therapies 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 prior to randomization.
  • Participant has at least one measurable LyM lesion confirmed by BIRC assessment prior to randomization.
  • Participants must be able to ingest study drug (either in tablet form or as a drinkable suspension \[Groups 1 to 4\] or granules or as an oral suspension \[Group 5\]) as assessed within 7 days before study treatment start. Drug administration via feeding tubes is allowed.

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Sequential
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

United States · 18 centers
  • UCSF Benioff Children s Hospital — Oakland
  • Childrens Hospital of Orange County — Orange
  • Lucile Packard Childrens Hosp — Palo Alto
  • Childrens National Medical Center — Washington D.C.
  • Nemours Childrens Clinic — Jacksonville
  • Childrens Hosp Boston Dept of Heme — Boston
  • WA Uni School Of Med — St Louis
  • UNC Chapel Hill — Chapel Hill
  • … and 10 more centers
France · 12 centers
  • Novartis Investigative Site — Angers
  • Novartis Investigative Site — Bordeaux
  • Novartis Investigative Site — Bron
  • Novartis Investigative Site — Caen
  • Novartis Investigative Site — Dijon
  • Novartis Investigative Site — Lille
  • Novartis Investigative Site — Marseille
  • Novartis Investigative Site — Montpellier
  • … and 4 more centers
Spain · 7 centers
  • Novartis Investigative Site — Palma
  • Novartis Investigative Site — Esplugues
  • Novartis Investigative Site — L'Hospitalet de Llobregat
  • Novartis Investigative Site — A Coruña
  • Novartis Investigative Site — Barcelona
  • Novartis Investigative Site — Madrid
  • Novartis Investigative Site — Madrid
Germany · 6 centers
  • Novartis Investigative Site — Freiburg im Breisgau
  • Novartis Investigative Site — Mannheim
  • Novartis Investigative Site — Cologne
  • Novartis Investigative Site — Leipzig
  • Novartis Investigative Site — Berlin
  • Novartis Investigative Site — Ulm
Italy · 6 centers
  • Novartis Investigative Site — Bologna
  • Novartis Investigative Site — Milan
  • Novartis Investigative Site — Roma
  • Novartis Investigative Site — Roma
  • Novartis Investigative Site — Torino
  • Novartis Investigative Site — Naples
Argentina · 3 centers
  • Novartis Investigative Site — CABA
  • Novartis Investigative Site — CABA
  • Novartis Investigative Site — Capital Federal
Australia · 3 centers
  • Novartis Investigative Site — Sydney
  • Novartis Investigative Site — Sydney
  • Novartis Investigative Site — Brisbane
Netherlands · 2 centers
  • Novartis Investigative Site — Nijmegen
  • Novartis Investigative Site — Rotterdam
Belgium · 1 center
  • Novartis Investigative Site — Brussels
Czechia · 1 center
  • Novartis Investigative Site — Brno
Switzerland · 1 center
  • Novartis Investigative Site — Lausanne

Identifiers

NCT: NCT05948943 · CBYL719P12201 · 2023-504146-60-00

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗