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) (EPIK-P2)

  • STATUS
    Recruiting
  • End date
    Dec 26, 2029
  • participants needed
    174
  • sponsor
    Novartis Pharmaceuticals
Updated on 23 September 2022
Investigator
Novartis Pharmaceuticals
Primary Contact
Novartis Investigative Site (7.2 mi away) Contact
+31 other location

Summary

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).

Description

This study consists of a screening period of up to 42 days, core period of 24 weeks, extension period of 24 weeks and long-term extension period of up to approximately 4 years. The study will enroll adult participants (Group 1), 6-17 years old pediatric participants (Group 2), and two exploratory sets of 2-5 years old pediatric participants (Group 3 treated with granules and Group 4 treated with film-coated tablets (FCT)). At study start, only the participants of Group 1 and Group 2 will be enrolled.

Eligible participants aged ≥6 years old will be randomized in a 2:1 ratio to alpelisib or matching placebo. Both age groups (group 1 and group 2) will be enrolled in the study in parallel. In the core period, participants will receive treatment in blinded fashion, with an upfront 16-week placebo-controlled period. After Week 16 those participants who were randomized to receive placebo will be switched to active treatment with alpelisib. Those participants who were randomized to receive alpelisib will continue their active treatment.

Participants in Group 4 will be enrolled before Group 3. All participants will received alpelisib in an open-label setting.

Group 3 will be enrolled later, after the completion of the primary analysis when the efficacy, safety and PK data will be available from the participants in Groups 1 and 2 in addition to the data from Group 4 as available, in order to select the recommended dose for participants in Group 3.

The planned duration of alpelisib treatment in the study will be up to 5 years after randomization/treatment start for all age groups. Participant may be discontinued from treatment with alpelisib earlier due to unacceptable toxicity, confirmed disease progression, death, and/or any other reason at the discretion of the investigator or the participant.

Details
Condition PIK3CA-related Overgrowth Spectrum (PROS)
Treatment Placebo, Alpelisib
Clinical Study IdentifierNCT04589650
SponsorNovartis Pharmaceuticals
Last Modified on23 September 2022

Eligibility

Yes No Not Sure

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
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
Other inclusion/exclusion criteria may apply
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
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
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