This is a Phase II multi-center study with an upfront 16-week, randomized, double-blind, placebo-controlled period, and extension periods, to assess the efficacy, safety and PK of alpelisib in pediatric and adult participants with PROS.
Child to Adult
Inclusion: 1. Signed informed consent and assent (when applicable) from the patient, parent, or guardian prior to any study related screening procedures are performed 2. Patients with diagnosis of PROS with symptomatic and /or progressive overgrowth and at least one measurable PROS-related lesion confirmed by blinded independent review committee (BIRC) assessment 3. Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local laboratories 4. A tissue sample must be available to be sent to a Novartis-designated central laboratory 5. Karnofsky (in patients > 16 years old at study entry)/Lansky (less than or equal to16 yrs of age at study entry) performance status index greater than or equal to 50 within 7 days before study treatment start 6. Adequate bone marrow and organ function including Fasting plasma glucose (FPG) less than or equal to 140 mg/dL (7.7 mmol/L)* and Glycosylated hemoglobin (HbA1c) less than or equal to 6.5% (both criteria have to be met) (as assessed by central laboratory for eligibility within 7 days before study treatment start) 7. Presence of at least one PROS-related measurable lesion defined as a lesion with longest diameter greater than or equal to 2 cm, when the volume can be accurately and reproducibly measured by MRI, and associated with complaints, clinical symptoms or functional limitations affecting the patient's everyday life. Measurability must be confirmed by BIRC before randomization. Exclusion: 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 2. Previous treatment with alpelisib and/or any other 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. Radiation exposure for PROS treatment purpose within the previous 12 months on those PROS areas which are expected to qualify for target lesions (except lesion(s) progressing after completion of radiotherapy) at time of informed consent. 4. Debulking or other major surgery performed within 3 months at time of informed consent 5. Clinically meaningful PROS-related thrombotic event (Grade 2 and more as per CTCAE v.4.03) within 30 days before informed consent, and/or sclerotherapy/embolization for vascular complications performed within 6 weeks before informed consent. Participants (receiving anticoagulants for PROS-related coagulopathy, primary or secondary prophylaxis of thrombosis may be included in the study) 6. Participants with documented pneumonitis or interstitial lung disease at time of informed consent 7. History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis at time of informed consent 8. Participants with an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at time of informed consent 9. Known history of seizure, or epilepsy, regardless of relatedness to PROS sprectrum at time of informed consent, when epilepsy is not controlled and/or the patient may not be switched to non-enzyme inducing antiepilectic drug(s) at time of informed consent.
Childrens Hospital Colorado
Taizo Nakano, MD
Protocol Number: 20-2825
More information available at ClinicalTrials.gov: NCT04589650
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