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 study on PIK3CA-Related Overgrowth Spectrum

Summary

Eligibility
for people ages 2-100 (full criteria)
Location
at Sacramento, California and other locations
Dates
study started
study ends around

Description

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).

Official Title

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

Details

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.

Keywords

PIK3CA-related Overgrowth Spectrum (PROS), Alpelisib (BYL719), Phase II, Adult, Pediatric, Adolescent, Alpelisib

Eligibility

You can join if…

Open to people ages 2-100

  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.

You CAN'T join if...

  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

Locations

  • Univ of California at Sacramento accepting new patients
    Sacramento California 95817 United States
  • Oregon Health Sciences University accepting new patients
    Portland Oregon 97239 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT06997588
Phase
Phase 2 PIK3CA-Related Overgrowth Spectrum Research Study
Study Type
Interventional
Participants
Expecting 140 study participants
Last Updated
Contact us about this trial