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Clinical Trials/NCT04980833
NCT04980833
Active, Not Recruiting
Phase 2

A Phase II Study to Evaluate the Long-term Safety and Efficacy of Alpelisib in Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Previously Participated in Study CBYL719F12002 (EPIK-P1)

Novartis Pharmaceuticals7 sites in 4 countries41 target enrollmentJanuary 27, 2022

Overview

Phase
Phase 2
Intervention
Alpelisib
Conditions
PIK3CA-related Overgrowth Spectrum (PROS)
Sponsor
Novartis Pharmaceuticals
Enrollment
41
Locations
7
Primary Endpoint
Prospective period only: Proportion of participants with new or worsening grade ≥3 treatment emergent adverse events (AEs)
Status
Active, Not Recruiting
Last Updated
2 months ago

Overview

Brief Summary

This is a prospective interventional Phase II multi center study, open label, preceded by a retrospective non-interventional period, to assess the long-term safety and efficacy of alpelisib, in pediatric and adult participants with PROS.

Detailed Description

The study will enroll males and females aged ≥2 years who previously participated in EPIK-P1 study and who continued to receive treatment with alpelisib after the cut-off date used in EPIK-P1 (NCT04285723). The study has an initial retrospective period and a subsequent prospective period. The retrospective period, is a non-interventional study period and will start one day after the EPIK-P1 data cut-off date (i.e. 10-Mar-2020). It will end the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Key safety and efficacy information that was previously collected as per local medical practice and recorded in the medical charts of eligible participants will be longitudinally abstracted. The prospective period, is an interventional study period and will start on the day of the first interventional dose administration in the prospective period. It will end after all participants have completed at least 5 years of treatment in the prospective period of the study or discontinued earlier, whichever occurs earlier. During this study period, safety and efficacy data will be prospectively collected following a structured plan that is common to all participants.

Registry
clinicaltrials.gov
Start Date
January 27, 2022
End Date
July 22, 2027
Last Updated
2 months ago
Study Type
Interventional
Study Design
Single Group
Sex
All

Investigators

Responsible Party
Sponsor

Eligibility Criteria

Inclusion Criteria

  • Participants who had previously participated in the study EPIK-P
  • Signed informed consent form and assent (when applicable) from the participant, parent, or guardian must be obtained prior to any study related screening procedures being performed.
  • Participant is treated with at least one dose of alpelisib after the EPIK-P1 study data cut- off date of 09-Mar-2020.

Exclusion Criteria

  • For participants in the retrospective period
  • \- All EPIK-P1 participants who permanently discontinued the investigational drug on or prior to the cut-off date 09-Mar-
  • For participants in the prospective period
  • Previous alpelisib treatment discontinuation (after 09-Mar-2020) due to any of the following adverse events:
  • Grade 4 skin and subcutaneous tissue disorders
  • Stevens-Johnson-Syndrome (SJS)/ Toxic Epidermal Necrolysis (TEN) or other SJS/TEN-like severe skin reactions (any grade)
  • Grade 4 hyperglycemia without confounding factors
  • Pneumonitis (any grade)
  • Grade 4 stomatitis
  • Grade 4 pancreatitis

Arms & Interventions

Alpelisib

All participants will receive alpelisib once a day

Intervention: Alpelisib

Outcomes

Primary Outcomes

Prospective period only: Proportion of participants with new or worsening grade ≥3 treatment emergent adverse events (AEs)

Time Frame: From date of first interventional dose administration in the prospective period (Day 1) to 30 days after last dose of study drug, assessed up to 5 years.

Incidence of new or worsening grade ≥3 treatment emergent AEs (by system organ class and preferred term)

Secondary Outcomes

  • Retrospective period: Proportion of participants with Adverse Events (AEs)(From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1))
  • Prospective period: Proportion of participants with AEs(From Day 1 up to 5 years)
  • Retrospective and prospective period: Overall clinical assessment as assessed by the investigator(Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years)
  • Retrospective and prospective period: Incidence of PROS-related symptoms and complications/comorbidities among participants with symptoms and complications/comorbidities.(Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years)
  • Retrospective and prospective period: Proportion of participants with healthcare visits/hospitalizations due to PROS.(Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years)
  • Retrospective and prospective period: Proportion of participants requiring PROS-related treatment(s) other than alpelisib(Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years)
  • Retrospective and prospective period: Proportion of participants with dose adjustments of alpelisib(Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years)
  • Retrospective and prospective period: Proportion of participants with PROS-related surgeries(Retrospective: From 10-Mar-2020 (1 day after EPIK-P1 data cut-off date) to the day before the first interventional dose of alpelisib is administered in the prospective period of this study (Day -1). Prospective: From Day 1 up to 5 years)

Study Sites (7)

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