Clinical trial NCT04980833: Study Assessing Long-term Safety and Efficacy of Alpelisib in Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Previously Participated in Study CBYL719F12002 (EPIK-P1)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: PIK3CA-related Overgrowth Spectrum (PROS)
Keywords: PIK3CA-related overgrowth spectrum (PROS)
Alpelisib
BYL719
Adult
Pediatric
Phase II
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-07-28
Enrollment: 41
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Participants who had previously participated in the study EPIK-P1.
* 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-2020.

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
  * Recurrent grade 4 thrombocytopenia
  * Grade 3 or 4 serum creatinine increase
  * Grade 4 isolated total bilirubin elevation
  * Recurrent grade 3 or 4 QT interval corrected by Fridericia's formula prolongation (\>500 ms or \>60 ms change from baseline)
* Known impairment of GI function due to concomitant disease that may significantly alter the absorption of the study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) at time of informed consent.
* Participant with uncontrolled diabetes mellitus (Type I or II) at time of informed consent.

Other inclusion/exclusion criteria may apply

Primary outcomes:
measure: Prospective period only: Proportion of participants with new or worsening grade ≥3 treatment emergent adverse events (AEs)
timeFrame: 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.
Secondary outcomes:
measure: Retrospective period: Proportion of participants with Adverse Events (AEs)
timeFrame: 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)
measure: Prospective period: Proportion of participants with AEs
timeFrame: From Day 1 up to 5 years
measure: Retrospective and prospective period: Overall clinical assessment as assessed by the investigator
timeFrame: 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
measure: Retrospective and prospective period: Incidence of PROS-related symptoms and complications/comorbidities among participants with symptoms and complications/comorbidities.
timeFrame: 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
measure: Retrospective and prospective period: Proportion of participants with healthcare visits/hospitalizations due to PROS.
timeFrame: 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
measure: Retrospective and prospective period: Proportion of participants requiring PROS-related treatment(s) other than alpelisib
timeFrame: 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
measure: Retrospective and prospective period: Proportion of participants with dose adjustments of alpelisib
timeFrame: 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
measure: Retrospective and prospective period: Proportion of participants with PROS-related surgeries
timeFrame: 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
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Childrens Hospital .
state: Massachusetts
city: Dijon
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris 15
country: France
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: