Trial Title:
Alpelisib in Pediatric and Adult Patients With Lymphatic Malformations Associated With a PIK3CA Mutation.
NCT ID:
NCT05948943
Condition:
Lymphatic Malformations
Conditions: Official terms:
Lymphangioma
Lymphatic Abnormalities
Congenital Abnormalities
Conditions: Keywords:
Cystic lymphangioma
Cystic hygroma
Lymphangioma circumscriptum
Cavernous lymphangioma
Lymphangioma
Macrocystic lymphatic malformation
Microcystic lymphatic malformation
Alpelisib
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description:
Stage 1 is open label. For adult and pediatric participants 6-17 years of age, Stage 2
comprises a 24-week double-blind period followed by an open-label period. For pediatric
participants 2-5 years of age, Stage 2 is open label.
Intervention:
Intervention type:
Drug
Intervention name:
Alpelisib
Description:
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 2-5 years of age will receive dose 3 of
alpelisib
Arm group label:
Adult participants, alpelisib (Stage 2)
Arm group label:
Adult participants, alpelisib dose 1 (Stage 1)
Arm group label:
Adult participants, alpelisib dose 2 (Stage 1)
Arm group label:
Pediatric participants (2-5 years of age), alpelisib (Stage 2)
Arm group label:
Pediatric participants (6-17 years of age), alpelisib (Stage 2)
Arm group label:
Pediatric participants (6-17 years of age), alpelisib dose 2 (Stage 1)
Arm group label:
Pediatric participants (6-17 years of age), alpelisib dose 3 (Stage 1)
Other name:
BYL719
Intervention type:
Drug
Intervention name:
Placebo
Description:
In Stage 2, participants will receive matching placebo for 24 weeks of the study
Arm group label:
Adult participants, placebo (Stage 2)
Arm group label:
Pediatric participants (6-17 years of age), placebo (Stage 2)
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.
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 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 to
alpelisib or placebo.
Additionally, in parallel, Stage 2 will include a 24-week open-label core phase in
pediatric participants 2-5 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 reviews.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
- 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.
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
Gender:
All
Minimum age:
2 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Lucile Packard Childrens Hosp .
Address:
City:
Palo Alto
Zip:
94304
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Joyce Teng
Email:
Principal Investigator
Facility:
Name:
WA Uni School Of Med Pediatric Hem-Onc
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Katie Schultz
Email:
Katie.schultz@wustl.edu
Investigator:
Last name:
Bryan Sisk
Email:
Principal Investigator
Facility:
Name:
Cinn Children Hosp Medical Center Cincinnati Childrens Hosp
Address:
City:
Cincinnati
Zip:
45229-3039
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amy Shova
Phone:
513-636-6090
Email:
Amy.Shova@cchmc.org
Investigator:
Last name:
Adrienne Hammill
Email:
Principal Investigator
Facility:
Name:
CHOP Abramson Pediatric Resch Ctr Oncology
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Samantha Santos
Email:
santoss3@chop.edu
Investigator:
Last name:
Denise Adams
Email:
Principal Investigator
Facility:
Name:
Baylor College Of Medicine
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nneka Uchendu
Phone:
713-798-3701
Email:
nxuchend@texaschildrens.org
Investigator:
Last name:
Ionela Iacobas
Email:
Principal Investigator
Facility:
Name:
Childrens Hospital and Regional Medical Center
Address:
City:
Seattle
Zip:
98105
Country:
United States
Status:
Recruiting
Contact:
Last name:
Maya Gopalan
Phone:
206-526-2100
Email:
maya.gopalan@seattlechildrens.org
Investigator:
Last name:
Jonathan A Perkins
Email:
Principal Investigator
Facility:
Name:
Novartis Investigative Site
Address:
City:
Brisbane
Zip:
4101
Country:
Australia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bruxelles
Zip:
1200
Country:
Belgium
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bordeaux Cedex
Zip:
33076
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bron Cedex
Zip:
69677
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Caen
Zip:
14033
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Lille
Zip:
59000
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Marseille
Zip:
13885
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Montpellier
Zip:
34295
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Paris cedex 10
Zip:
75010
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Tours 9
Zip:
37044
Country:
France
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Mannheim
Zip:
68305
Country:
Germany
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Freiburg
Zip:
79106
Country:
Germany
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Koeln
Zip:
50937
Country:
Germany
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Leipzig
Zip:
04103
Country:
Germany
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bologna
Zip:
40138
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Milano
Zip:
20122
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Roma
Zip:
00165
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Roma
Zip:
00168
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Napoli
Zip:
80129
Country:
Italy
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Esplugues De Llobregat
Zip:
08950
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Status:
Recruiting
Start date:
November 24, 2023
Completion date:
November 28, 2031
Lead sponsor:
Agency:
Novartis Pharmaceuticals
Agency class:
Industry
Source:
Novartis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05948943
