PIK3CA-related Overgrowth Spectrum (PROS)Phase 2NCT06997588
EPIK-P4: A Phase II Single-arm Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)
A Phase 2 study testing Alpelisib in people with PIK3CA-related Overgrowth Spectrum (PROS), run by Novartis Pharmaceuticals at 39 sites in 11 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 2 to 100 years
- Conditions the study is for
- PIK3CA-related Overgrowth Spectrum (PROS)
- What is being tested?
- Alpelisib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 39 sitesin 11 countries
- Study dates
- 9 Oct 2025to 18 Jun 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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 ≥50.
- 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.
Who cannot join
- 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 2 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 15 days before study treatment initiation, 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 15 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
Trial locations and contacts
39 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
39 sites in 11 countries
United States9 sites, 9 recruiting
- Recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Miriam Davis, miriam.davis@unc.edu
Alexandra Borst
- Recruiting
Cinn Children Hosp Medical Center
Cincinnati, Ohio, 45229-3039
Sarah Price, 513-636-7374, Sarah.Price@cchmc.org
Adrienne Hammill
- Recruiting
Nationwide Children s Hospital
Columbus, Ohio, 43205
Star Seum, star.seum@nationwidechildrens.org
Bhuvana Setty
- Recruiting
Baylor College Of Medicine
Houston, Texas, 77030
Gaylon Stevenson, 713-798-3701, gnsteve1@texaschildrens.org
Netta Schneller
- Recruiting
UT Health Science Center
Houston, Texas, 77030
Annette Frenk, 713-500-6654, annette.c.frenkoquendo@uth.tmc.edu
Autumn Atkinson
- Recruiting
Childrens Hosp Pittsburgh UPMC
Pittsburgh, Pennsylvania, 15224
Alex Berkebile, 412-692-5346, berkebileak@upmc.edu
Julia Segal
- Recruiting
Oregon Health Sciences University
Portland, Oregon, 97239
Annie Yang, 503-494-5742, yangann@ohsu.edu
Melinda Wu
- Recruiting
Childrens Hospital and Regional Medical Center
Seattle, Washington, 98105
Shing Varakitsomboon, 206-526-2100, shing.varakitsomboon@seattlechildrens.org
Juliana Bonilla-Velez
- Recruiting
Washington University
St Louis, Missouri, 63110
Catie Knoerle, knoerlec@wustl.edu
Bryan Sisk
France7 sites, 7 recruiting
- Recruiting
Novartis Investigative Site
Angers, 49933
- Recruiting
Novartis Investigative Site
Bron, 69677
- Recruiting
Novartis Investigative Site
Dijon, 21000
- Recruiting
Novartis Investigative Site
Montpellier, 34295
- Recruiting
Novartis Investigative Site
Paris, 75015
- Recruiting
Novartis Investigative Site
Toulouse, 31400
- Recruiting
Novartis Investigative Site
Tours, 37044
Germany6 sites, 6 recruiting
- Recruiting
Novartis Investigative Site
Berlin, 13353
- Recruiting
Novartis Investigative Site
Düsseldorf, North Rhine-Westphalia, 40225
- Recruiting
Novartis Investigative Site
Freiburg im Breisgau, Baden-Wurttemberg, 79106
- Recruiting
Novartis Investigative Site
Halle, Saxony-Anhalt, 06120
- Recruiting
Novartis Investigative Site
Leipzig, Saxony, 04103
- Recruiting
Novartis Investigative Site
Stuttgart, 70374
Spain4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
A Coruña, 15006
- Recruiting
Novartis Investigative Site
Barcelona, 08035
- Recruiting
Novartis Investigative Site
Esplugues, Barcelona, 08950
- Recruiting
Novartis Investigative Site
Madrid, 28046
Australia3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
North Adelaide, South Australia, 5066
- Recruiting
Novartis Investigative Site
Sydney, New South Wales, 2010
- Recruiting
Novartis Investigative Site
Sydney, New South Wales, 2031
Italy3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Roma, RM, 00168
- Recruiting
Novartis Investigative Site
Torino, TO, 10126
- Recruiting
Novartis Investigative Site
Trieste, TS, 34137
Austria2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Salzburg, 5020
- Recruiting
Novartis Investigative Site
Vienna, 1090
United Kingdom2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Liverpool, L12 2AP
- Recruiting
Novartis Investigative Site
London, WC1N 3JH
Netherlands1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Nijmegen, 6525 GA
Switzerland1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Lausanne, 1011
About this study
Official title: Study Assessing the Efficacy, Safety and Pharmacokinetics of Alpelisib in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)
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).
Read the detailed description
The study consists of 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.
Extension 2 Period: Participants will continue their treatment under the same rules as the core and Extension 1 periods until the last participant completes the Extension 2 period. Participants still deriving clinical benefit from alpelisib at the end of the study may receive post-trial access (PTA) to alpelisib.
- Being tested
- Alpelisib
- Keywords
- PIK3CA-related overgrowth spectrum (PROS), Alpelisib (BYL719), Phase II, Adult, Pediatric, Adolescent
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlpelisibDrug
Also called BYL719
Oral Film-Coated Tablet (FCT):
- Group 1: 250 mg once daily
- Group 2, 6 to <18 years: 125 mg once daily (starting dose)
Granules:
- Group 2, 2 to <6 years: 50 mg once daily (starting dose)
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Adult participants ≥18 years of age. Receives: Drug: Alpelisib |
| Group 2 | Experimental | Children and adolescents 2 to <18 years of age. Receives: Drug: Alpelisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with a confirmed objective response by BIRC
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.
Measured: Up to Week 48
Secondary outcomes (18)
Proportion of participants with a confirmed objective response by BIRC in a protocol-defined subset of patients
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.
Measured: Up to Week 48
Change from baseline (as assessed by BIRC) in target lesion volume
Change from baseline (as assessed by BIRC) in target lesion volume will be summarized descriptively
Measured: 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
Change from baseline (as assessed by BIRC) in MRI-measurable non-target lesion volume will be summarized descriptively
Measured: 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
Change from baseline (as assessed by BIRC) in all MRI-measurable (target and non-target) lesion volume will be summarized descriptively
Measured: 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
Change from baseline (as assessed by BIRC) in other non-target lesion will be summarized descriptively
Measured: 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)
Appearance of new lesions (as assessed by BIRC) will be summarized descriptively
Measured: 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
Measured: 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)
Duration of response (DOR) is defined as the time from the first documented confirmed objective response until progression of any PROS lesion by BIRC or death or rescue surgery for any PROS lesion.
Measured: From first documented response until progression of PROS lesions or death, assessed up to approximately 3 years
Alpelisib plasma concentration
Measured: 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)
Two items from the Brief Pain Inventory (BPI) will be used for adult and pediatric participants aged 12 years and older. The first item assesses the worst pain intensity in the past 24 hours, with responses on an 11-point scale from 0 (no pain) to 10 (pain as bad as you can imagine). The second item evaluates pain interference with general activity in the past 24 hours, also on an 11-point scale from 0 (does not interfere) to 10 (completely interferes).
Measured: 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
For children aged 3-11 years, the Wong-Baker FACES® Pain Rating Scale will be used instead of the BPI worst pain intensity question. This scale features six faces showing increasing levels of pain, each with a numeric rating and a descriptor (from 0 'no hurt' to 10 'hurts worst'). Children will select the face that best represents their pain level. There is no pain intensity scale for children under 3 years.
Measured: 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)
A Patient Global Impression of Symptom Severity (PGI-S) item will be used to understand the overall severity of symptoms experienced and clinical meaningfulness of treatment effects experienced during this study. This item includes 5 response options: no symptoms, mild, moderate, severe, and very severe. This scale can be completed by the parent/caregiver for pediatric participants aged <12 years.
Measured: 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)
Time to Treatment Failure (TTF) is defined as the time from alpelisib treatment start date until disease progression supported by radiological assessment performed by BIRC, death, rescue surgery for any PROS lesion or discontinuation of alpelisib due to any reason other than technical problems or study termination by the sponsor. Participants who complete the study, are ongoing treatment or discontinue alpelisib due to technical problems (e.g. drug supply issues, site prematurely ends study participation) or study termination by the sponsor will be censored at the date of last study treatment received.
Measured: From Baseline up to approximately 3 years
Overall Clinical Response
The proportion of participants with overall clinical response reported as improvement, stable or worsening of clinical condition, as assessed by the Investigator will be summarized descriptively.
Measured: From Baseline up to approximately 3 years
Change from Baseline in symptoms and complications/comorbidities associated with PROS
Changes in symptoms and complications/comorbidities (i.e., walking impairment, cardiac/pulmonary/renal function, pain, Karnofsky/Lansky performance status) will be summarized descriptively. For each complication/comorbidity, only participants who have this reported as being present at baseline will be included in the analysis. When new symptoms/complications/comorbidities appear at any time of study therapy, they will be assessed for clinical significance and reported as adverse events when applicable.
Measured: From Baseline up to approximately 3 years
Percentage of participants with healthcare visits/hospitalized due to PROS
Percentage of participants with healthcare visit/hospitalized due to PROS will be assessed for Group 1 and Group 2.
Measured: Up to at least 3 years
Percentage of participants with surgeries required to manage PROS
Percentage of participants requiring rescue surgery due to PROS will be assessed for Group 1 and Group 2.
Measured: Up to at least 3 years
Number of Adverse Events and Serious Adverse Events as assessed by CTCAE criteria
Treatment emergent Adverse Event (TEAEs) in this study were events that started after the first dose of study treatment and until 30 days after the last dose of study treatment, or events present prior to the first dose of treatment which increased in severity based on preferred term within 30 days after the last study treatment.
Measured: Up to at least 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2025
- Study start9 Oct 2025
- Primary completion29 Jan 2029 (estimated)
- Study completion18 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PIK3CA-related Overgrowth Spectrum (PROS)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06997588
- Sponsor's protocol ID
- CBYL719F12202
- Other IDs
- 2024-519960-42-00
- Status last verified
- Oct 2026
- First submitted
- 21 May 2025
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study Assessing the Efficacy, Safety and Pharmacokinetics of Alpelisib in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)
- ClinicalTrials.gov ID
- NCT06997588
- Acronym / sponsor ID
- CBYL719F12202
- Keywords
- PIK3CA-related overgrowth spectrum (PROS), Alpelisib (BYL719), Phase II, Adult, Pediatric, Adolescent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2025 (actual)
- Primary completion
- 29 Jan 2029 (estimated)
- Study completion
- 18 Jun 2031 (estimated)
- First posted
- 30 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The study consists of 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.
Extension 2 Period: Participants will continue their treatment under the same rules as the core and Extension 1 periods until the last participant completes the Extension 2 period. Participants still deriving clinical benefit from alpelisib at the end of the study may receive post-trial access (PTA) to alpelisib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: AlpelisibAdult participants ≥18 years of age. |
| Group 2 | Experimental | Drug: AlpelisibChildren and adolescents 2 to <18 years of age. |
Who may qualify
- Ages
- 2 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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 ≥50.
- PGI-S score of mild, moderate, severe, or very severe at screening.
Key exclusion criteria (8 listed)
- 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 2 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 15 days before study treatment initiation, and/or sclerotherapy/embolization for vascular complications performed within 6 weeks before informed consent/assent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlpelisibAlso: BYL719Oral Film-Coated Tablet (FCT): * Group 1: 250 mg once daily * Group 2, 6 to <18 years: 125 mg once daily (starting dose) Granules: • Group 2, 2 to <6 years: 50 mg once daily (starting dose) | Drug | Group 1, Group 2 |
Primary outcome
Proportion of participants with a confirmed objective response by BIRC
Time frame: 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.
18 secondary outcomes
Proportion of participants with a confirmed objective response by BIRC in a protocol-defined subset of patients
Time frame: Up to Week 48
Change from baseline (as assessed by BIRC) in target lesion volume
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: From first documented response until progression of PROS lesions or death, assessed up to approximately 3 years
Alpelisib plasma concentration
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: From Baseline up to approximately 3 years
Overall Clinical Response
Time frame: From Baseline up to approximately 3 years
Change from Baseline in symptoms and complications/comorbidities associated with PROS
Time frame: From Baseline up to approximately 3 years
Percentage of participants with healthcare visits/hospitalized due to PROS
Time frame: Up to at least 3 years
Percentage of participants with surgeries required to manage PROS
Time frame: Up to at least 3 years
Number of Adverse Events and Serious Adverse Events as assessed by CTCAE criteria
Time frame: Up to at least 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
39 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alpelisib in people with PIK3CA-related Overgrowth Spectrum (PROS), run by Novartis Pharmaceuticals at 39 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 39 sites in United States, France, Germany, Spain, Australia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Novartis Pharmaceuticals (1-888-669-6682, novartis.email@novartis.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with a confirmed objective response by BIRC (time frame: Up to Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.