Home › Trials › NCT06997588

Alpelisib for children and adults with PIK3CA-related overgrowth spectrum (PROS)

Study Assessing the Efficacy, Safety and Pharmacokinetics of Alpelisib in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)

Phase 2 Interventional Novartis · NCT06997588

This project will try daily oral alpelisib to see if it reduces overgrowth and improves symptoms in children and adults with PROS.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment104 (estimated)
Ages2 Years to 100 Years
SexAll
SponsorNovartis Industry-sponsored
Drugs / interventionsRadiation
Locations30 sites (St Louis, Missouri and 29 other locations)
Trial IDNCT06997588 on ClinicalTrials.gov

What this trial studies

This is an open-label, single-arm Phase II trial giving daily oral alpelisib to pediatric and adult participants with PROS to measure efficacy, safety, tolerability, and pharmacokinetics. Screening (up to 42 days) includes confirmation of a somatic PIK3CA mutation and a whole-body MRI to document lesions. The core treatment period lasts 48 weeks with adults starting at 250 mg once daily and children dosed by age (50 mg for ages 2–<6 and 125 mg for ages 6–<18), followed by extension periods totaling up to two years of additional follow-up. Outcomes include change in overgrowth-related measures, adverse events, and drug exposure over time.

Who should consider this trial

Good fit: Ideal candidates are people aged 2 years or older with symptomatic, progressive PROS, a documented somatic PIK3CA mutation, and adequate performance status who can undergo required imaging and biopsies.

Not a fit: People without a documented PIK3CA mutation, those with only isolated macrodactyly, macrocephaly or epidermal nevus, or those with medical conditions that contraindicate alpelisib or the required procedures are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, alpelisib could reduce abnormal tissue growth and improve function and quality of life for people with PROS.

How similar studies have performed: Small case series and early-phase reports have shown promising responses to alpelisib in PROS, but large randomized data are still limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

1. Male or female participants aged ≥2 years at the time of informed consent/assent.
2. 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.
3. 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.
4. Karnofsky (in participants \>16 years of age at study entry) or Lansky (≤16 years of age at study entry) performance status index ≥50.
5. PGI-S score of mild, moderate, severe, or very severe at screening.
6. Adequate bone marrow and organ function.
7. 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.

Key Exclusion Criteria:

1. 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.
2. 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 4 weeks prior to the first dose of study medication with alpelisib).
3. Debulking or other major surgery performed within 3 months at the time of informed consent/assent.
4. Radiation exposure for PROS treatment purpose within 12 months prior to informed consent/assent.
5. Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per CTCAE v4.03) within 30 days before informed consent/assent, and/or sclerotherapy/embolization for vascular complications performed within 6 weeks before informed consent/assent.
6. Clinically meaningful bleeding from PROS-related lesion (Grade 2 and more as per CTCAE v4.03) within 30 days before study treatment initiation.
7. 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

Where this trial is running

St Louis, Missouri and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions PIK3CA-related Overgrowth SpectrumPIK3CA-related overgrowth spectrumAlpelisibPhase IIAdultPediatricAdolescent
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.