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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) (EPIK-P3)

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ClinicalTrials.gov Identifier: NCT04980833
Recruitment Status : Not yet recruiting
First Posted : July 28, 2021
Last Update Posted : July 28, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
PIK3CA-related Overgrowth Spectrum (PROS) Drug: Alpelisib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : September 30, 2021
Estimated Primary Completion Date : October 27, 2027
Estimated Study Completion Date : October 27, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Alpelisib
All participants will receive alpelisib once a day
Drug: Alpelisib
Participant's treatment plan has been established by the treating physician, within the global compassionate use framework. Doses permitted are 50, 125, 200 and 250 mg.
Other Name: BYL719




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Retrospective period: Proportion of participants with Adverse Events (AEs) [ Time Frame: 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) ]
    Incidence, type and severity per common terminology criteria for AEs (CTCAE) v4.03 criteria, causality assessments of AEs, including changes in laboratory values, vital signs and assessment of cardiac function during the retrospective period.

  2. Prospective period: Proportion of participants with AEs [ Time Frame: From Day 1 up to 5 years ]
    Incidence, type and severity per CTCAE v4.03 criteria, causality assessments of AEs, including changes in laboratory values, vital signs, assessment of cardiac function, and growth, sexual maturation and bone/dental development (for applicable age) during the prospective period.

  3. Retrospective and prospective period: Overall clinical assessment as assessed by the investigator [ Time Frame: 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 ]
    Proportion of participants with overall clinical assessment reported as improvement, stable or worsened, as assessed by the investigator.

  4. Retrospective and prospective period: Incidence of PROS-related symptoms and complications/comorbidities among participants with symptoms and complications/comorbidities. [ Time Frame: 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 ]
    Incidence of symptoms and complications/comorbidities (including taken treatment measures) associated with PROS over time among participants with symptoms and complications/comorbidities.

  5. Retrospective and prospective period: Proportion of participants with healthcare visits/hospitalizations due to PROS. [ Time Frame: 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 ]
    Proportion of participants with healthcare visits/hospitalizations due to PROS will be assessed.

  6. Retrospective and prospective period: Proportion of participants requiring PROS-related treatment(s) other than alpelisib [ Time Frame: 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 ]
    Proportion of participants requiring PROS-related treatment(s) other than alpelisib, including medications (concomitant PROS-related medications including medication for the management of PROS related complications as well as medications to manage complications secondary to alpelisib) and non-drug treatments (e.g., feeding tube, ketogenic diet, non-invasive device for sleep apnea, sclerotherapy, endovascular occlusive procedures)

  7. Retrospective and prospective period: Proportion of participants with dose adjustments of alpelisib [ Time Frame: 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 ]
    Proportion of participants requiring dose increase, reductions and interruptions of alpelisib

  8. Retrospective and prospective period: Proportion of participants with PROS-related surgeries [ Time Frame: 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 ]
    Proportion of participants requiring surgery due to PROS



Information from the National Library of Medicine

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04980833


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04980833    
Other Study ID Numbers: CBYL719F12401
First Posted: July 28, 2021    Key Record Dates
Last Update Posted: July 28, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
PIK3CA-related overgrowth spectrum (PROS)
Alpelisib
BYL719
Adult
Pediatric
Phase II