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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 2 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 15 days before study treatment initiation, 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 15 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 it's running

• Univ of California at Sacramento
  Sacramento, California, United States Recruiting
• Childrens National Medical Center
  Washington D.C., District of Columbia, United States Recruiting
• Washington University
  St Louis, Missouri, United States Recruiting
• University of North Carolina at Chapel Hill
  Chapel Hill, North Carolina, United States Recruiting
• Cinn Children Hosp Medical Center
  Cincinnati, Ohio, United States Recruiting
• Nationwide Children s Hospital
  Columbus, Ohio, United States Recruiting

Study contacts

• Study coordinator: Novartis Pharmaceuticals
• Email: novartis.email@novartis.com
• Phone: 1-888-669-6682

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Evaluating CYH33 for PIK3CA-related overgrowth and vascular malformations

  This study is testing a new treatment called CYH33 to see if it can help people with PIK3CA-related overgrowth and vascular problems feel better and have fewer side effects.

  Recruiting at 14 sites Phase 1/2 Haihe Biopharma Co., Ltd. · Beijing, Beijing Municipality and 14 other locations · NCT06975618

• Treatment for PIK3CA-related overgrowth and malformations using RLY-2608

  This study is testing a new treatment called RLY-2608 to see if it can help adults and children with PIK3CA-related overgrowth and malformations feel better.

  Recruiting at 40 sites Phase 2 Relay Therapeutics, Inc. · Phoenix, Arizona and 39 other locations · NCT06789913

• Targeted therapies for patients with vascular malformations

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• Examining Proteus Syndrome and Related Congenital Disorders

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.