Retrospective Chart Review Study of Patients With PIK3CA-Related Overgrowth Spectrum Who Have Received Alpelisib (EPIK-P1)

• ClinicalTrials.gov Identifier: NCT04285723
• Recruitment Status: Completed
• First Posted: February 26, 2020
• Last Update Posted: May 17, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The study is a site-based retrospective non-interventional medical chart review of pediatric and adult male and female patients with PIK3CA-Related Overgrowth Spectrum (PROS). Patient-level data are abstracted from medical charts of all eligible patients at all participating sites.

Information from patients treated with alpelisib will be used to describe the efficacy and safety of alpelisib in PROS patients.

Condition or disease
PIK3CA-Related Overgrowth Spectrum (PROS)

Study Design

• Study Type: Observational
• Actual Enrollment: 59 participants
• Observational Model: Case-Only
• Time Perspective: Retrospective
• Official Title: Retrospective Chart Review Study of Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Have Received Alpelisib as Part of a Compassionate Use Program (EPIK-P1)
• Actual Study Start Date: June 9, 2020
• Actual Primary Completion Date: April 16, 2021
• Actual Study Completion Date: April 16, 2021

Groups and Cohorts

Group/Cohort
alpelisib; Patients treated with alpelisib

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with response (yes/no) at Week 24 (+/- 4 weeks) [ Time Frame: 24 weeks (+/- 4 weeks) ]
   Proportion of patients with response (yes/no) at Week 24 (+/- 4 weeks), defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions.

Secondary Outcome Measures :

1. Percent change in the sum of measurable target lesion volume as measured by the change between the index date and key time-points following the index date [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]
   Percent change in the sum of measurable target lesion (1 to 3 lesions) volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 12 weeks prior) and key time-points following the index date
2. Percent change in the sum of all measurable (target and non-target) lesion volume between the index date (or up to 12 weeks prior) and key time-points following the index date [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]
   Percent change in the sum of all measurable (target and non-target) lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 12 weeks prior) and key time-points following the index date
3. Description of medications and non-drug therapy received at key time points [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

   Description of medications and non-drug therapy received at key time points

   • PROS-related treatment(s) other than alpelisib
   • Medication(s) (e.g., concomitant PROS-related medications including medication for the management of PROS related complications as well as medications to manage complications secondary to alpelisib)
   • Non-drug treatment(s) (e.g., feeding tube, ketogenic diet, non-invasive device for sleep apnea, sclerotherapy, endovascular occlusive procedures)
   • Alpelisib treatment (e.g., dose, dose adjustments, duration of treatment, dose interruptions, discontinuation)
   • PROS-related surgeries (e.g., de-bulking or vascular surgery as well as the intended site of the procedure)
4. Change in PROS symptoms and complications over time [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

   Change in PROS symptoms and complications over time

   • Overgrowth lesions, including number, girth, size, and color
   • Life-threatening complications (e.g., stroke, pulmonary embolism)
   • Chronic bleeding/leaking
   • Infection episodes
   • Hypotonia
   • Sleep disturbances
   • Seizures
   • Thrombotic events
   • Thromboembolic events
   • Pain
   • Cognitive impairment
   • Fatigue
   • Migraines
   • Depression/anxiety
5. Change in functional status (work/school attendance) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

   Change in functional status

   o Work/school/pre-school attendance

6. Change in health care resource use [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

   Change in health care resource use

   • Non-medical resource use (e.g., physical therapy, occupational therapy, home care services)
   • Hospitalizations (including relevant medical interventions undertaken if related to PROS)
   • ER visits (including relevant medical interventions undertaken
7. Change in laboratory assessments [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]
   Change in laboratory assessments (e.g., D-dimer, fibrinogen, hemoglobin, renal function, albumin, protein)
8. Type, frequency, seriousness, and severity per CTCAE v4.03 criteria and causality assessments of treatment-emergent adverse events [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

   Type, frequency, seriousness, and severity per CTCAE v4.03 criteria and causality assessments of treatment-emergent adverse events

   o Adverse events, including start and end date, grade, seriousness, relation to treatment, action taken with study treatment, and outcome

9. Percent change in the sum of all measurable non-target lesion volume between the index date (or up to 12 weeks prior) and key time-points following the index date [ Time Frame: 4, 12, 24, 3, 52 weeks after starting the study treatment (index date) ]
   Percent change in the sum of all measurable non-target lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 12 weeks prior) and key time-points following the index date
10. Change in functional status (mobility) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

    Change in functional status

    o Mobility measured with an Investigator developed scale.

11. Change in functional status (performance status) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

    Change in functional status

    o ECOG performance status

12. Change in assessments of cardiac function [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]
    Change in cardiac assessments (e.g. ECG)
13. Change in clinical assessments (height) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

    Change in clinical assessments

    o Vital signs (height)

14. Change in clinical assessments (blood pressure) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

    Change in clinical assessments

    o Vital signs (blood pressure)

15. Change in clinical assessments (weight) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

    Change in clinical assessments

    o Vital signs (weight)

16. Change in clinical assessments (resting pulse) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

    Change in clinical assessments

    o Vital signs (resting pulse)

17. Change in functional status (performance status) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

    Change in functional status

    o Lansky performance status

18. Change in functional status (performance status) [ Time Frame: 4, 12 , 24, 36, 52 weeks after starting the study treatment (index date) ]

    Change in functional status

    o Karnofsky performance status

19. Duration of response [ Time Frame: At the time of the cutoff date 9 March 2020 ]
    Duration of response defined as the time from first documented response, to the date of the first documented disease progression or death due to any cause.

Eligibility Criteria

• Ages Eligible for Study: 2 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patients who participated in the compassionate use program and received alpelisib for the treatment of PIK3CA-related overgrowth spectrum (PROS).

Criteria

Inclusion Criteria:

• Patient (adult or pediatric) is ≥ 2 years of age *
• Patient has a physician confirmed/documented diagnosis of PROS*
• Patient has a documented evidence of a mutation in the PIK3CA gene*
• Patient's condition was assessed by the treating physician as severe or life threatening and treatment was deemed necessary*
• Patient has been treated with at least one dose of alpelisib, initiated on or before 23-Sep-2019 (i.e. at least 24 weeks before the cut-off date of the 09-Mar-2020)
• Patient has medical chart history available during enrollment in the Novartis MAP
• Patient (or parent/guardian in case of pediatric patient) consented to participate in the study (as required by local ethics regulations) * Inclusion criteria for MAP enrollment (assessed at the time of alpelisib initiation)

Contacts and Locations

Locations

United States, Massachusetts

Boston Childrens Hospital

Boston, Massachusetts, United States, 02215

Australia, Victoria

Novartis Investigative Site

Parkville, Victoria, Australia, 3052

France

Novartis Investigative Site

Montpellier cedex 5, Herault, France, 34059

Novartis Investigative Site

Dijon, France, 21000

Novartis Investigative Site

Paris cedex 15, France, 75015

Ireland

Novartis Investigative Site

Dublin, Ireland, 12

Spain

Novartis Investigative Site

Madrid, Spain, 28046

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04285723
• Other Study ID Numbers: CBYL719F12002
• First Posted: February 26, 2020
• Last Update Posted: May 17, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

alpelisib; PIK3CA; BYL719; PROS; Retrospective chart review study; EPIK-P1