Alpelisib for Overgrowth Spectrum Disorders

(EPIK-P3 Trial)

Not currently recruiting at 9 trial locations

Overseen By Novartis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Alpelisib

Disqualifiers: Uncontrolled diabetes, GI impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the long-term safety and effectiveness of alpelisib, a medication for people with PROS, a group of conditions causing tissue overgrowth. Participants will take alpelisib daily to evaluate its efficacy and safety over time. The trial seeks individuals who participated in the EPIK-P1 study and continued using alpelisib after March 9, 2020. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that alpelisib is likely to be safe for humans?

Research has shown that alpelisib is generally safe for treating PROS, a condition related to abnormal growths. In one study, about 82 out of 100 patients experienced some side effects. For about 39 out of 100 patients, these side effects were directly linked to the treatment. The most common issues were mild, such as an upset stomach or a skin rash.

However, some serious risks exist. Alpelisib can cause lung problems, such as lung inflammation, which is rare but can be life-threatening and requires immediate medical attention.

Overall, while most people tolerate alpelisib well, some risks remain. Discussing with a doctor how this treatment might affect an individual is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about alpelisib for overgrowth spectrum disorders because it targets a specific pathway known as PI3K, which is often overactive in these conditions. This is different from traditional treatments that primarily focus on managing symptoms rather than addressing the underlying cause. Alpelisib's targeted approach could potentially offer more effective control over the disorder's progression, providing a new avenue for treatment beyond the standard care options.

What evidence suggests that alpelisib might be an effective treatment for PROS?

Research has shown that alpelisib can help treat PROS (PIK3CA-Related Overgrowth Spectrum). In one study, 37.5% of patients improved after six months of treatment. Alpelisib blocks a specific pathway that causes abnormal cell growth. Another study found that while not everyone responded, some patients experienced a noticeable decrease in the size of their vascular malformations. This suggests alpelisib could be a promising option for managing symptoms and reducing growth issues in affected individuals. ^{5 6 7 8 9}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for pediatric and adult patients with PIK3CA-Related Overgrowth Spectrum (PROS) who were previously in the EPIK-P1 study. They must have taken at least one dose of alpelisib after March 9, 2020, and give informed consent. People can't join if they stopped taking alpelisib due to severe side effects or have certain medical conditions like uncontrolled diabetes.

Inclusion Criteria

Participant is treated with at least one dose of alpelisib after the EPIK-P1 study data cut-off date of 09-Mar-2020

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

Exclusion Criteria

I stopped taking alpelisib due to severe side effects or uncontrolled diabetes.

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

Timeline for a Trial Participant

Retrospective Period

Non-interventional period where key safety and efficacy information is collected from medical charts

From 10-Mar-2020 to Day -1

Prospective Period

Interventional period where participants receive alpelisib and safety and efficacy data are collected

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Alpelisib

Trial Overview

The study is testing the long-term safety and effectiveness of a drug called Alpelisib in treating PROS. It's an open-label Phase II trial where all participants know they're getting Alpelisib, following up on earlier research from the EPIK-P1 study.

How Is the Trial Designed?

Group I: Alpelisib Experimental Treatment 1 Intervention

All participants will receive alpelisib once a day

Alpelisib is already approved in United States, European Union for the following indications:

Approved in United States as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen

Approved in European Union as Piqray for:

• Hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer in combination with fulvestrant

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a study using genome-wide CRISPR activation screens on neuroblastoma cell lines, PIM1 was identified as a resistance gene that, when overexpressed, is linked to poor survival outcomes in patients with ALK-positive neuroblastoma.

Combining the ALK inhibitor ceritinib with the PIM1 inhibitor AZD1208 significantly enhances anti-tumor efficacy in patient-derived xenografts, suggesting that targeting both ALK and PIM1 could be an effective treatment strategy for high-risk neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The targetable kinase PIM1 drives ALK inhibitor resistance in high-risk neuroblastoma independent of MYCN status. Trigg, RM., Lee, LC., Prokoph, N., et al.[2021]

Alpelisib received accelerated FDA approval for treating severe PIK3CA-related overgrowth spectrum (PROS) in patients aged 2 years and older, based on real-world data from a study involving 37 patients, where 27% showed a significant radiologic response after 24 weeks.

Among those who responded to treatment, 60% maintained their response for at least 12 months, indicating potential long-term benefits, although common side effects included diarrhea, stomatitis, and hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Alpelisib for PIK3CA-related Overgrowth Spectrum (PROS). Singh, S., Bradford, D., Li, X., et al.[2023]

In a phase 1 study involving 44 pediatric patients with refractory solid tumors and ALCL, the recommended phase 2 dose (RP2D) of crizotinib in combination with topotecan and cyclophosphamide was determined to be 215 mg/m2/dose taken twice daily, showing it can be safely tolerated at this dosage.

The study found that while the oral solution of crizotinib was not well tolerated due to palatability issues, the crizotinib formulated capsules were more acceptable, although they led to increased toxicity that requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and pharmacokinetics of crizotinib in combination with cytotoxic chemotherapy for pediatric patients with refractory solid tumors or anaplastic large cell lymphoma (ALCL): a Children's Oncology Group phase 1 consortium study (ADVL1212). Greengard, E., Mosse, YP., Liu, X., et al.[2021]

PF-06463922 is a next-generation ALK inhibitor that shows significantly higher potency than crizotinib against various ALK mutations, including those that confer resistance, such as F1174L and F1245C.

In preclinical studies, PF-06463922 induced complete tumor regression in both crizotinib-resistant and sensitive neuroblastoma models, suggesting it could be a promising treatment option for children with ALK-mutated neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Infarinato, NR., Park, JH., Krytska, K., et al.[2022]

Citations

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37634128/

Alpelisib for treatment of patients with PIK3CA-related ...

Results: Twenty-four weeks (6 months) after treatment initiation, 12 of 32 (37.5%) patients with complete case records included in the analysis of the primary ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S1098360023009851

Alpelisib for treatment of patients with PIK3CA-related ...

Alpelisib, a PI3Kα-selective inhibitor, targets the underlying etiology of PROS, offering a novel therapeutic approach to current management strategies.

3.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-alpelisib-pik3ca-related-overgrowth-spectrum

FDA approves alpelisib for PIK3CA-related overgrowth ...

The major efficacy outcome measure was the proportion of patients with radiological response at week 24 as determined by blinded independent ...

4.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/5512/527723/Epik-P2-A-Phase-2-Study-of-Alpelisib-ALP-in

Epik-P2: A Phase 2 Study of Alpelisib (ALP) in Pediatric and ...

The primary objective was not met; confirmed objective response with ALP (any time) was achieved in 16.7% (9/54; 97.5% CI: 7.0%-31.1%) and 23.2% ...

5.

nature.com

nature.com/articles/s41431-025-01885-y

First report of successful pregnancies after treatment with ...

Alpelisib was associated with symptoms improvement and reduction in the vascular malformation volume as assessed by MRI (Fig. 2A, B). After 23 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10841299/

Alpelisib for PIK3CA-related Overgrowth Spectrum (PROS)

The safety profile of alpelisib is acceptable in view of the severe and potentially life-threatening nature of PROS as a rare disease and the lack of FDA- ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2022/215039Orig1s000RiskR.pdf

Division of Risk Management (DRM) - accessdata.fda.gov

BYL719C2301 (SOLAR-1) provided the safety data of treatment combination of alpelisib (Piqray) 300 mg. q.d. with fulvestrant 500 mg i.m ...

8.

mayoclinic.org

mayoclinic.org/drugs-supplements/alpelisib-oral-route/description/drg-20465046

Alpelisib (oral route) - Side effects & dosage

This medicine may cause swelling of the lungs (pneumonitis) or interstitial lung disease. These are life-threatening conditions and require ...

9.

sciencedirect.com

sciencedirect.com/science/article/pii/S2405844024035606

A real-world disproportionality analysis of FDA adverse ...

Our research scrutinizes the FDA database to assess alpelisib 's safety. We retrospectively analyzed data from April 2019 to June 2023 using ...