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NCT04285723: EPIK-P1

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

Completed Results posted Last updated 9 February 2023
What this trial tests

trial testing alpelisib in PIK3CA-Related Overgrowth Spectrum (PROS) in 57 participants. Completed in 16 April 2021.

Timeline
9 June 2020
Primary endpoint
16 April 2021
16 April 2021

Quick facts

Lead sponsorNovartis Pharmaceuticals
StatusCompleted
Study typeOBSERVATIONAL
Enrollment57
Start date9 June 2020
Primary completion16 April 2021
Estimated completion16 April 2021
Sites7 locations across France, Ireland, Australia, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

2 and older, any sex, with PIK3CA-Related Overgrowth Spectrum (PROS). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Patients Responders and Non-responders at Week 24 Primary · Index date and week 24 or 6 months (± 4 weeks)

Response is 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.

Responders
GroupValue95% CI
Pediatric Patients30.413.2 – 52.9
Adult Patients55.621.2 – 86.3
Non Responders
GroupValue95% CI
Pediatric Patients69.647.1 – 86.8
Adult Patients44.413.7 – 78.8
Percent Change in the Sum of Measurable Target Lesion Volume Secondary · Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187)

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 24 weeks prior) and key time-points following the index date. The index date: (baseline) was defined as the date of alpelisib initiation End of study: patients were followed up to a maximum of 187 weeks.

4 weeks
GroupValue95% CI
Pediatric Patients-11.64± 12.869
Adult Patients-11.78± 8.154
12 weeks
GroupValue95% CI
Pediatric Patients-18.59± 16.837
Adult Patients-19.77± 5.128
24 weeks
GroupValue95% CI
Pediatric Patients-11.20± 19.987
Adult Patients-19.69± 15.375
52 weeks
GroupValue95% CI
Pediatric Patients-13.91± 19.206
Adult Patients-6.52± 2.614
End of study
GroupValue95% CI
Pediatric Patients-36.47± 46.137
Adult Patients-17.38± 11.679
Percent Change in the Sum of All Measurable Lesion Volume Secondary · Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187)

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 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. End of study: patients were followed up to a maximum of 187 weeks As no measurable non-target lesions were identified, the results for changes in the sum of all measurable (target and non-target) lesion volume were identical to the results presented for measurable targe

4 weeks
GroupValue95% CI
Pediatric Patients-11.64± 12.869
Adult Patients-11.78± 8.154
12 weeks
GroupValue95% CI
Pediatric Patients-18.59± 16.837
Adult Patients-19.77± 5.128
24 weeks
GroupValue95% CI
Pediatric Patients-11.20± 19.987
Adult Patients-19.69± 15.375
52 weeks
GroupValue95% CI
Pediatric Patients-13.91± 19.206
Adult Patients-6.52± 2.614
End of study
GroupValue95% CI
Pediatric Patients-36.47± 46.137
Adult Patients-17.38± 11.679
Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments Secondary · Up to 187 weeks

Number of participants with concomitant PIK3CA Related Overgrowth Spectrum (PROS)-related non-drug treatments and other medical interventions by reason for discontinuation. A patient may have multiple information, but was counted only once in type of other supportive non-drug treatment if more than one type in this category has been reported.

Recovery
GroupValue95% CI
Pediatric Patients12
Adult Patients2
Completed the planned course of treatment
GroupValue95% CI
Pediatric Patients4
Adult Patients7
Unknown
GroupValue95% CI
Pediatric Patients2
Adult Patients1
Lack of efficacy
GroupValue95% CI
Pediatric Patients1
Adult Patients1
Other
GroupValue95% CI
Pediatric Patients2
Adult Patients0
Adverse event
GroupValue95% CI
Pediatric Patients0
Adult Patients1
Progressive disease
GroupValue95% CI
Pediatric Patients0
Adult Patients1
Subject decision
GroupValue95% CI
Pediatric Patients0
Adult Patients1
Participants With Concomitant PROS-related Medications Over Time Secondary · Index date, week 24 and end of study

Number of participants with at least one concomitant utilization of PIK3CA Related Overgrowth Spectrum (PROS)-related medication. End of study: patients were followed up to a maximum of 187 weeks. Results are provided for the full study population as planned and documented in the protocol and SAP, and not by age group.

Index date
GroupValue95% CI
All Patients34
24 weeks
GroupValue95% CI
All Patients30
End of study
GroupValue95% CI
All Patients25
Number of PROS-related Completed Surgeries During the Study Period Secondary · Up to 187 weeks

Number of surgeries by reason of surgery. A patient may have multiple anatomical sites of surgery and types of surgery on the same day.

Other
GroupValue95% CI
Pediatric Patients4
Adult Patients2
Disease improvement
GroupValue95% CI
Pediatric Patients2
Adult Patients1
Disease progression (not radiologically confirmed)
GroupValue95% CI
Pediatric Patients3
Adult Patients0
Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms Secondary · Index date and week 24 or 6 months (± 4 weeks)

Improvement in PIK3CA Related Overgrowth Spectrum (PROS) signs and symptoms was defined based on Common Toxicity Criteria (CTC) grade reduction or resolution of the event from index date. CTC is a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. The Common Terminology Criteria for Adverse Events (CTCAE) system is a product of the US National Cancer Institute (NCI). For this study, version 4.03 was used

Fatigue improved by week 24
GroupValue95% CI
Pediatric Patients22
Adult Patients10
Vascular malformation improved by week 24
GroupValue95% CI
Pediatric Patients20
Adult Patients10
Disseminated intravascular coagulation improved by week 24
GroupValue95% CI
Pediatric Patients11
Adult Patients5
Limb asymmetry improved by week 24
GroupValue95% CI
Pediatric Patients11
Adult Patients9
Pain improved by week 24
GroupValue95% CI
Pediatric Patients11
Adult Patients9
Change in Performance Status Score Secondary · Index date and week 24 or 6 months (± 4 weeks)

Participants with a change in performance status score (ECOG, Karnofsky, Lansky) between the index date and week 24. Patients completed one questionnaire (ECOG, Karnofsky or Lansky) based on physicians choice. The Eastern Cooperative Oncology Group (ECOG) score runs from 0 to 5, with 0 denoting perfect health and 5 death. The Karnofsky Performance Score (KPS) and Lansky score run from 0 to 100, where 0 is death and 100 is perfect health. For the ECOG scale, "improvement" is defined as a decrease by at least 1 point and and "worsening" is defined as an increase by at least 1 point. For the Ka

GroupValue95% CI
Pediatric Patients9
Adult Patients1
Pediatric Patients8
Adult Patients6
Pediatric Patients0
Adult Patients0
Pediatric Patients16
Adult Patients7
Functional Status - Mobility Assessment Secondary · Up to 187 weeks

Change in functional status: Mobility severity assessment measured up to the judgment of the investigator. A patient may have multiple information

GroupValue95% CI
Pediatric Patients0
Adult Patients1
Pediatric Patients0
Adult Patients1
Pediatric Patients1
Adult Patients2
Pediatric Patients0
Adult Patients1
Change From Index Date in Functional Status - School Status During the Study Period Secondary · Index date, week 24 and end of study (up to 187 weeks)

Change in functional status: School status during the study period (no attendance, part-time or full time). Improvement is defined as a shift from reporting of "No attendance" to "Part-time" as well as , "Part-time" or "No attendance" to "Full-time"; Worsening is defined as a shift from reporting of "Part-time" to "No attendance", as well as from "Full-time" to "Part-time" or "No attendance". If neither of the criteria for improvement or worsening is met, then it is considered stable.

Change 24 weeks
GroupValue95% CI
Pediatric Patients1
Adult Patients0
Pediatric Patients28
Adult Patients4
Pediatric Patients0
Adult Patients0
Pediatric Patients0
Adult Patients0
End of study
GroupValue95% CI
Pediatric Patients2
Adult Patients2
Pediatric Patients27
Adult Patients2
Pediatric Patients0
Adult Patients0
Pediatric Patients0
Adult Patients0
Change From Index Date in Functional Status - Work Status Secondary · Index date, week 24 and end of study

Change in functional status: Work status assessment during the study period (no attendance, part-time, full-time or unemployed). Improvement is defined as a shift from reporting of "No attendance" to "Part-time" or "Full time", from "Part-time" to "Full-time", as well as from "Unemployed" to "Part-time" or "Full-time" work. Worsening is defined as a shift from reporting of "Part-time" to "No attendance", "Full-time" to "Part-time" or "No attendance" as well as "Part-time" or "Full-time" to "Unemployed" status. Change in score is only applicable if both index date and post-index date informa

Change 24 weeks
GroupValue95% CI
Adult Patients0
Adult Patients1
Adult Patients6
Adult Patients1
Change end of study
GroupValue95% CI
Adult Patients5
Adult Patients0
Adult Patients2
Adult Patients1
Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient Secondary · Up to 187 weeks

Hospitalizations starting on or after the start of study treatment (index date) or starting prior to and continuing after the start of study treatment are summarized.

Number of times a patient has been hospitalized
GroupValue95% CI
Pediatric Patients1.8± 1.03
Adult Patients1.7± 0.82
Number of times a patient has been hospitalized due to PROS
GroupValue95% CI
Pediatric Patients1.1± 0.35
Adult Patients1.0± 0.00

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment or cut-off date whichever occurs first, up to maximum duration of 187 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pediatric Patients
Serious: 10/39 (26%)
Deaths: 0/39
Adult Patients
Serious: 11/18 (61%)
Deaths: 0/18

Serious adverse events (34 terms)

ReactionSystemPediatric PatientsAdult Patients
Vascular malformationCongenital, familial and genetic disorders
Gait disturbanceGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Disseminated intravascular coagulationBlood and lymphatic system disorders
Adrenal insufficiencyEndocrine disorders
VolvulusGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Impaired healingGeneral disorders
InflammationGeneral disorders
CellulitisInfections and infestations
InfluenzaInfections and infestations
Otitis media acuteInfections and infestations
Streptococcal sepsisInfections and infestations
Urinary tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
Multiple fracturesInjury, poisoning and procedural complications
Post procedural discomfortInjury, poisoning and procedural complications
Pulmonary contusionInjury, poisoning and procedural complications
AcidosisMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Haematoma muscleMusculoskeletal and connective tissue disorders
LipomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (67 terms — click to expand)

ReactionSystemPediatric PatientsAdult Patients
DiarrhoeaGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
Aphthous ulcerGastrointestinal disorders
StomatitisGastrointestinal disorders
InflammationGeneral disorders
HypoglycaemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
AlopeciaSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
EczemaSkin and subcutaneous tissue disorders
Disseminated intravascular coagulationBlood and lymphatic system disorders
Vascular malformationCongenital, familial and genetic disorders
HaemorrhoidsGastrointestinal disorders
Viral infectionInfections and infestations
Memory impairmentNervous system disorders
Skin ulcerSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
CoagulopathyBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
HyperparathyroidismEndocrine disorders
HypothyroidismEndocrine disorders
Abdominal painGastrointestinal disorders
Anal fissureGastrointestinal disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
ToothacheGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Gait disturbanceGeneral disorders
Abscess soft tissueInfections and infestations
BronchitisInfections and infestations
CellulitisInfections and infestations
CystitisInfections and infestations
ErysipelasInfections and infestations
NasopharyngitisInfections and infestations
Prostatitis Escherichia coliInfections and infestations
Soft tissue infectionInfections and infestations
Urinary tract infectionInfections and infestations
Weight decreasedInvestigations

Most-reported serious reactions: Vascular malformation, Gait disturbance, Pain in extremity, Disseminated intravascular coagulation, Adrenal insufficiency, Volvulus, Vomiting, Fatigue.

Data from ClinicalTrials.gov NCT04285723 adverse events section.

Sponsor's own description

The study was a site-based retrospective non-interventional medical chart review of pediatric and adult male and female patients with PIK3CA-Related Overgrowth Spectrum (PROS) who initiated alpelisib at least 24 weeks before the cut-off date at a MAP site. The study cut-off date was 09-Mar-2020. Patient-level data were abstracted from medical charts of all eligible patients at all participating sites. Study completion date refers to the last date data was extracted. Information from patients treated with alpelisib was used to describe the efficacy and safety of alpelisib in PROS patients.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations.
    Canaud G, Hammill AM, Adams D, Vikkula M, et al · · 2021 · cited 122× · PMID 34238334 · DOI 10.1186/s13023-021-01929-8
  2. Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS).
    Canaud G, Lopez Gutierrez JC, Irvine AD, Vabres P, et al · · 2023 · cited 56× · PMID 37634128 · DOI 10.1016/j.gim.2023.100969
  3. Treatment of two infants with PIK3CA-related overgrowth spectrum by alpelisib.
    Morin G, Degrugillier-Chopinet C, Vincent M, Fraissenon A, et al · · 2022 · cited 44× · PMID 35080595 · DOI 10.1084/jem.20212148
  4. FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum.
    Singh S, Bradford D, Li X, Mishra-Kalyani PS, et al · · 2024 · cited 32× · PMID 37624421 · DOI 10.1158/1078-0432.ccr-23-1270
  5. Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth.
    Wenger TL, Ganti S, Bull C, Lutsky E, et al · · 2022 · cited 32× · PMID 36066547 · DOI 10.1016/j.gim.2022.07.026
  6. PIK3CA gain-of-function mutation in adipose tissue induces metabolic reprogramming with Warburg-like effect and severe endocrine disruption.
    Ladraa S, Zerbib L, Bayard C, Fraissenon A, et al · · 2022 · cited 28× · PMID 36490341 · DOI 10.1126/sciadv.ade7823
  7. Targeted therapy for capillary-venous malformations.
    Zerbib L, Ladraa S, Fraissenon A, Bayard C, et al · · 2024 · cited 21× · PMID 38880808 · DOI 10.1038/s41392-024-01862-9
  8. PIK3CA inhibition in models of proliferative glomerulonephritis and lupus nephritis.
    Yamaguchi J, Isnard P, Robil N, de la Grange P, et al · · 2024 · cited 14× · PMID 38842935 · DOI 10.1172/jci176402

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Other trials of alpelisib

Trials testing the same drug.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04285723.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing