PIK3CA-related Overgrowth Spectrum (PROS)Phase 2EPIK-P3NCT04980833
Study Assessing Long-term Safety and Efficacy of Alpelisib in Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Previously Participated in Study CBYL719F12002 (EPIK-P1)
A Phase 2 study testing Alpelisib in people with PIK3CA-related Overgrowth Spectrum (PROS), run by Novartis Pharmaceuticals at 6 sites in 4 countries.
Trial summary
This Phase II, multicenter, open-label study, preceded by a retrospective non-interventional period, is assessing the long-term safety and efficacy of alpelisib in pediatric and adult 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
- 41 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 27 Jan 2022to 22 Jun 2027
- Phase
- Phase 2
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
- Participants who had previously participated in the study EPIK-P1.
- Signed informed consent form and assent (when applicable) from the participant, parent, or guardian must be obtained prior to any study related screening procedures being performed.
- Participant is treated with at least one dose of alpelisib after the EPIK-P1 study data cut- off date of 09-Mar-2020.
Who cannot join
- For participants in the retrospective period
- All EPIK-P1 participants who permanently discontinued the investigational drug on or prior to the cut-off date 09-Mar-2020.
- For participants in the prospective period
- Previous alpelisib treatment discontinuation (after 09-Mar-2020) due to any of the following adverse events:
- Grade 4 skin and subcutaneous tissue disorders
- Stevens-Johnson-Syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN) or other SJS/TEN-like severe skin reactions (any grade)
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- Grade 4 hyperglycemia without confounding factors
- Pneumonitis (any grade)
- Grade 4 stomatitis
- Grade 4 pancreatitis
- Recurrent grade 4 thrombocytopenia
- Grade 3 or 4 serum creatinine increase
- Grade 4 isolated total bilirubin elevation
- Recurrent grade 3 or 4 QT interval corrected by Fridericia's formula prolongation (>500 ms or >60 ms change from baseline)
- Known impairment of GI function due to concomitant disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) at time of informed consent.
- Participant with uncontrolled diabetes mellitus (Type I or II) at time of informed consent.
- Other inclusion/exclusion criteria may apply
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
France3 sites
Novartis Investigative Site
Dijon, 21000
Novartis Investigative Site
Montpellier, 34295
Novartis Investigative Site
Paris, 75015
United States1 site
Boston Childrens Hospital
Boston, Massachusetts, 02215
About this study
Official title: A Phase II Study to Evaluate the Long-term Safety and Efficacy of Alpelisib in Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Previously Participated in Study CBYL719F12002 (EPIK-P1)
This Phase II, multicenter, open-label study, preceded by a retrospective non-interventional period, is assessing the long-term safety and efficacy of alpelisib in pediatric and adult participants with PIK3CA-related overgrowth spectrum (PROS).
Read the detailed description
The study will enroll male and female participants aged 2 years or older who previously participated in the EPIK-P1 study (NCT04285723) and continued to receive alpelisib after the EPIK-P1 data cut-off date of 09 March 2020.
The study consists of an initial retrospective period followed by a prospective period.
The retrospective, non-interventional period began on 10 March 2020, one day after the EPIK-P1 data cut-off date, and ended the day before the participant received the first interventional dose of alpelisib in the prospective period. Safety and efficacy data collected during routine medical practice were longitudinally abstracted from participants' medical records.
The prospective, interventional period began on the day the participant received the first interventional dose of alpelisib. Safety and efficacy data are being collected according to a structured assessment plan common to all participants. The prospective period will end after all participants have completed at least 5 years of treatment or discontinued treatment earlier, whichever occurs first.
- Being tested
- Alpelisib
- Keywords
- PIK3CA-Related Overgrowth Spectrum (PROS), Alpelisib, BYL719, PIK3CA Mutation, Overgrowth Disorders, Adult, Pediatric, Phase II, Long-term Safety, Long-term Efficacy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlpelisibDrug
Also called BYL719
Retrospective period: Participants receive alpelisib under a Temporary Authorization for Use (ATU) or Managed Access Program (MAP) according to the treatment plan established by the treating physician. The recommended starting dose is 50 mg orally once daily for pediatric participants and 250 mg orally once daily for adult participants. Pediatric treatment interruptions and adult dose adjustments are permitted for toxicity.
Prospective period: Participants receive alpelisib orally once daily with food. The starting dose is generally based on the last dose received during the retrospective period. Participants transitioning from fasted to fed administration may start at an adjusted dose. Dose escalation for response optimization and dose reduction or interruption for safety or tolerability are permitted. Dose escalation above 250 mg is not allowed. Treatment is planned for at least 5 years or until earlier discontinuation.
| Study group | Role | What they receive |
|---|---|---|
| Alpelisib | Experimental | All participants receive alpelisib orally once daily during the prospective period. Treatment is planned for at least 5 years or until earlier discontinuation. Receives: Drug: Alpelisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prospective period only: Proportion of participants with new or worsening grade ≥3 treatment emergent adverse events (AEs)
Incidence of new or worsening grade ≥3 treatment emergent AEs (by system organ class and preferred term)
Measured: From first interventional dose administration in the prospective period (Day 1) until treatment discontinuation, assessed for at least 5 years; participants not entering a Novartis rollover study undergo a 30-day safety follow-up after the last dose.
Secondary outcomes (8)
Retrospective period: Proportion of participants with Adverse Events (AEs)
Incidence, type and severity per CTCAE v4.03 criteria, causality assessments of AEs, including changes in laboratory values, vital signs and cardiac function during the retrospective period.
Measured: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period (Day -1)
Prospective period: Proportion of participants with AEs
Incidence, type and severity per CTCAE v4.03 criteria, causality assessments of AEs, including changes in laboratory values, vital signs, cardiac function, and growth, sexual maturation, and bone/dental development (for applicable ages).
Measured: From first interventional dose administration in the prospective period (Day 1) until treatment discontinuation, assessed for at least 5 years
Retrospective and prospective period: Overall clinical assessment as assessed by the investigator
Proportion of participants with overall clinical assessment reported as improvement, stable or worsened, as assessed by the investigator.
Measured: Retrospective: From 10-Mar-2020 to Day -1. Prospective: From Day 1 until treatment discontinuation, assessed for at least 5 years.
Retrospective and prospective period: Incidence of PROS-related symptoms and complications/comorbidities among participants with symptoms and complications/comorbidities.
Incidence of symptoms and complications/comorbidities associated with PROS among affected participants.
Measured: Retrospective: From 10-Mar-2020 to Day -1. Prospective: From Day 1 until treatment discontinuation, assessed for at least 5 years.
Retrospective and prospective period: Proportion of participants with healthcare visits/hospitalizations due to PROS.
Proportion of participants with healthcare visits/hospitalizations due to PROS.
Measured: Retrospective: From 10-Mar-2020 to Day -1. Prospective: From Day 1 until treatment discontinuation, assessed for at least 5 years
Retrospective and prospective period: Proportion of participants requiring PROS-related treatment(s) other than alpelisib
Proportion of participants requiring PROS-related treatment(s) other than alpelisib, including medications (concomitant PROS-related medications including medication for the management of PROS related complications as well as medications to manage complications secondary to alpelisib) and non-drug treatments (e.g., feeding tube, ketogenic diet, non-invasive device for sleep apnea, sclerotherapy, endovascular occlusive procedures)
Measured: Retrospective: From 10-Mar-2020 to Day -1. Prospective: From Day 1 until treatment discontinuation, assessed for at least 5 years
Retrospective and prospective period: Proportion of participants with dose adjustments of alpelisib
Proportion of participants requiring dose increase, reductions and interruptions of alpelisib
Measured: Retrospective: From 10-Mar-2020 to Day -1. Prospective: From Day 1 until treatment discontinuation, assessed for at least 5 years
Retrospective and prospective period: Proportion of participants with PROS-related surgeries
Proportion of participants requiring surgery due to PROS
Measured: Retrospective: From 10-Mar-2020 to Day -1. Prospective: From Day 1 until treatment discontinuation, assessed for at least 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2021
- Study start27 Jan 2022
- Primary completion22 Jun 2027 (estimated)
- Study completion22 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
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
- NCT04980833
- Sponsor's protocol ID
- CBYL719F12401
- Other IDs
- 2023-508522-95-00, 2023
- Acronym
- EPIK-P3
- Status last verified
- Sep 2026
- First submitted
- 19 Jul 2021
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- 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
Publications
Cheng YL, Bustamante D, Yates DM, Menendez S, Chi AC. TEK-related venous malformation of the orofacial region: report of a case with multidisciplinary treatment guided by molecular diagnosis. Oral Surg Oral Med Oral Pathol Oral Radiol. 2025 Nov;140(5):587-593. doi: 10.1016/j.oooo.2025.05.009. Epub 2025 Jun 6.
PubMed 40603171