Study Assessing the Efficacy, Safety and PK of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum

EPIK-P2: A Phase II Double-blind Study With an Upfront, 16-week Randomized, Placebo-controlled Period, to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)

ClinicalTrials.gov Identifier: NCT04589650

Novartis Reference Number: CBYL719F12201

Last Update: Sep 07, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

This is a prospective 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 pharmacokinetics of alpelisib in pediatric and adult participants with PIK3CA-related overgrowth spectrum (PROS).

Condition 
PIK3CA-related Overgrowth Spectrum (PROS)
Phase 
Phase 2
Overall status 
Recruiting
Start date 
Apr 19, 2021
Completion date 
Dec 26, 2029
Gender 
All
Age(s)
2 Years and older (Child, Adult, Older Adult)

Interventions

Drug
Alpelisib
Adult participants (group 1) will receive 125 mg of alpelisib oral tablets once daily. Pediatric participants (Group 2: 6 to 17 years old) will receive 50 mg of alpelisib oral tablets once daily. Pediatric participants (Group 4: 2 to 5 years old) will receive 50 mg of alpelisib oral tablets once daily, Pediatric participants (Group 3: 2 to 5 years old) will receive alpelisib granules at dose determined based on the primary analysis for efficacy, safety and PK of alpelisib in Groups 1 and 2 in addition to the data from Group 4 as available.
Drug
Placebo
Participants will receive matching placebo once daily up to week 16.

Eligibility Criteria

Inclusion Criteria:

Signed informed consent and assent (when applicable) from the patient, parent, legal authorized representative or guardian prior to any study related screening procedures are performed
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
Documented evidence of a somatic mutation(s) in the PIK3CA gene performed in local laboratories

A tissue sample (fresh or archival) is be sent to a Novartis-designated central laboratory. If archival tissue is not available, collection of a fresh tissue biopsy is required for participants in Groups 1 and 2, if it is not clinically contraindicated. For participants in Groups 3 and 4, a fresh tissue biopsy is not mandatory.

For China only: Tissue sample collection and biomarker assessments are not applicable.

For Germany only: If archival tissue is available, it must be sent to a Novartis designated central laboratory. If no archival tissue is available, obtaining a fresh tissue biopsy is recommended, if it is not clinically contraindicated, but is not mandatory.

Karnofsky (in patients > 16 years old at study entry)/Lansky (≤16 yrs of age at study entry) performance status index ≥50
Adequate bone marrow and organ function including Fasting plasma glucose (FPG) ≤ 140 mg/dL (7.7 mmol/L) and Glycosylated hemoglobin (HbA1c) ≤ 6.5% (both criteria have to be met) (as assessed by central laboratory for eligibility)
Presence of at least one PROS-related measurable lesion defined as a lesion with longest diameter ≥2 cm, when the volume can be accurately and reproducibly measured by MRI (Magnetic resonance imaging), and associated with complaints, clinical symptoms or functional limitations affecting the patient's everyday life. Measurability must be confirmed by BIRC before randomization.

Exclusion Criteria:

Participant with only isolated macrodactyly, skin 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
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)
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.
Debulking or other major surgery performed within 3 months at time of informed consent
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. Note: Participants receiving anticoagulants for PROS-related coagulopathy, primary or secondary prophylaxis of thrombosis may be included in the study
Participants in Groups 1 and 2 with documented pneumonitis or interstitial lung disease at time of informed consent and with impaired lung function (e.g., FEV1 or DLCO ≤ 70% of predicted) that is not related to PROS. Participants in Groups 3 and 4 with documented or suspicious pneumonitis or interstitial lung disease based on MRI images at time of informed consent
History of acute pancreatitis within 1 year before informed consent or past medical history of chronic pancreatitis at time of informed consent
Participants with an established diagnosis of type I diabetes mellitus or uncontrolled type II diabetes mellitus at time of informed consent
Known history of seizure, or epilepsy, regardless of relatedness to PROS spectrum at time of informed consent, when epilepsy is not controlled and/or the patient may not be switched to non-enzyme inducing antiepileptic drug(s) at time of informed consent.

Other inclusion/exclusion criteria may apply

Study Locations

United States
UCLA Medical Center
Recruiting
Los Angeles, 90095 - California
Contact: Vivian Y Chang
United States
Childrens Hospital Colorado
Recruiting
Aurora, 80045 - Colorado
Contact: Andrew Morin (720-777-5379) - [email protected] - Taizano Nakano
United States
Childrens Healthcare of Atlanta
Recruiting
Atlanta, 30342 - Georgia
Contact: Gabrielle Dean (404-785-8700) - [email protected] - Michael Briones D O
United States
Washington University
Recruiting
Saint Louis, 63110 - Missouri
Contact: Yvette Schulz - [email protected] - Bryan Sisk
United States
UNC Chapel Hill
Recruiting
Chapel Hill, 27599 - North Carolina
Contact: Miriam Davis (919-966-0985) - [email protected] - Julie Blatt
United States
Cincinnati Children s Hospital Medical Center
Recruiting
Cincinnati, 45229-3039 - Ohio
Contact: Cincinnati HVMC Research Staff (513-803-4862) - [email protected] - Adrienne Hammill
United States
CHOP Abramson Pediatric Resch Ctr
Recruiting
Philadelphia, 19104 - Pennsylvania
Contact: Bede Nriagu - [email protected] - Denise Adams
United States
University of Texas Southwestern Medical Center
Recruiting
Dallas, 75235 - Texas
Contact: Teresa Banda (214-456-5413) - [email protected] - Kathleen Ludwig
United States
Children's Hospital and Regional Medical Center
Recruiting
Seattle, 98105 - Washington
Contact: Dhanashree Sawant (206-526-2100) - [email protected] - Jonathan A Perkins
United States
University of Wisconsin Hospital and Clinics
Recruiting
Madison, 53792 - Wisconsin
Contact: Ashley Ng (608-890-8070) - [email protected] - Carol Diamond
United States
Canada
Novartis Investigative Site
Recruiting
Toronto, M5G 1X8
Ontario
Canada
Novartis Investigative Site
Recruiting
Montreal, H2W 1T8
Quebec
Canada
Novartis Investigative Site
Recruiting
Montreal, H3T 1C5
Quebec
Canada
China
Novartis Investigative Site
Recruiting
Shanghai, 200011
-
China
France
Novartis Investigative Site
Recruiting
Bordeaux Cedex, 33076
-
France
Novartis Investigative Site
Recruiting
Dijon, 21000
-
France
Novartis Investigative Site
Recruiting
Paris cedex 15, 75015
-
France
Novartis Investigative Site
Recruiting
Tours cedex 9, 37044
-
France
Germany
Novartis Investigative Site
Recruiting
Duesseldorf, 40225
-
Germany
Novartis Investigative Site
Recruiting
Freiburg, 79106
-
Germany
Novartis Investigative Site
Recruiting
Hamburg, 22149
-
Germany
Novartis Investigative Site
Recruiting
Heidelberg, 69120
-
Germany
Novartis Investigative Site
Recruiting
Leipzig, 04103
-
Germany
Hong Kong
Novartis Investigative Site
Recruiting
Pokfulam,
-
Hong Kong
Italy
Novartis Investigative Site
Recruiting
Roma, 00165
RM
Italy
Netherlands
Novartis Investigative Site
Recruiting
Nijmegen, 6525EX
-
Netherlands
Norway
Novartis Investigative Site
Recruiting
Oslo, 0372
-
Norway
Spain
Novartis Investigative Site
Recruiting
Esplugues de Llobregat, 08950
Barcelona
Spain
Novartis Investigative Site
Recruiting
Madrid, 28046
-
Spain
Switzerland
Novartis Investigative Site
Recruiting
Bern, 3010
-
Switzerland
Novartis Investigative Site
Recruiting
Zuerich, CH - 8032
-
Switzerland
United Kingdom
Novartis Investigative Site
Recruiting
London, SW17 0QT
-
United Kingdom
Novartis Investigative Site
Recruiting
Manchester, M13 9WL
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

Have a question?

Call 1-888-669-6682 or email [email protected]