Sirolimus Effect on Hypertrophic Syndromes Related Gene PIK3CA
PROMISE
Non-randomised Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Due to PIK3CA- Related Overgrowth
1 other identifier
interventional
16
1 country
11
Brief Summary
It was found that people who have an excessive growth in one or more parts of their body and normal growth in other parts, may have a change in genes responsible for controlling cell growth. This genetic discovery identified a possible treatment for this overgrowth, called Sirolimus. This is a pilot study, which help the investigators prepare a larger international study, which will aim to determine whether a treatment based Sirolimus is able to stop the excessive growth of one or more parties of their body in people who carry a genetic change in the PIK3CA gene (phosphatidylinosilol-3-kinase encoded by the gene PIK3CA).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started May 2015
Shorter than P25 for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2015
CompletedFirst Submitted
Initial submission to the registry
May 4, 2015
CompletedFirst Posted
Study publicly available on registry
May 14, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2016
CompletedNovember 21, 2025
November 1, 2025
1.5 years
May 4, 2015
November 18, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Measure of the relative percentage of the excess tissue volume evolution at the affected site by volumetric MRI.
Change from baseline at 6 and 12 months
Secondary Outcomes (4)
Measure sites of overgrowth by DXA, MRI and circumferential measurements
Change from baseline at 6 and 12 months
To determine optimal sirolimus dosing algorithms by plasma assay
12 months
Number of hospitalisation and surgery
12 months
quality of life measured by a questionnaire in the pre- and post-treatment periods
At 6 and 12 months
Interventions
Low dose sirolimus will be given in daily dosing to achieve trough levels of 2-6 ng/ ml.
Eligibility Criteria
You may qualify if:
- Post-zygotic PIK3CA mutation
- Age: 3-65 years
- Measurable overgrowth, in current progression or with clinical history of overgrowth progression
- Patient clinically stable
- Presence of a disability, social or cosmetic impairment requiring treatment from the patient perspective,
- Written informed consent form signed and dated by the subject or by the patient's legal representative
You may not qualify if:
- Pregnancy or lactation
- Women and men of reproductive age without any effective method of contraception (during treatment and up to 12 weeks after sirolimus discontinuation)
- Hypersensitivity to the active substance (sirolimus) or to any of the excipients
- Impossibility to obtain written informed consent form signed by the subject or the patient's legal representative, or vulnerable adults
- Treatment with Sirolimus in the last 4 weeks before the trial
- Personal history of malignancy or current investigations for suspected malignancy
- Active skin infection requiring antibiotics or antiviral treatments
- HIV or hepatitis B or C infection
- Past history of Mycobacterium tuberculosis infection
- Active pneumopathy
- Uncontrolled infection
- Chronic liver disease (ASAT or Alanine amino transférase (ALAT)\> 3 times upper normal limit)
- Stage 3 (or more) chronic renal insufficiency (eGFR\< 60mls/min)
- Neutropenia with neutrophiles \< 1.0 x10\^9/L
- Uncontrolled dyslipidemia
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
CHU d'Angers
Angers, 49933, France
CHU de Bordeaux - GH Pellegrin
Bordeaux, 33076, France
CHU de DIJON
Dijon, 21079, France
Hôpital Jeanne de Flandre
Lille, 59037, France
CHRU de Montpellier - Hôpital Saint-Eloi
Montpellier, 34295, France
Hopitaux de Brabois Chu Nancy
Nancy, 54511, France
Hôpital mère-enfant de Nantes
Nantes, 44093, France
CHU Paris - Necker
Paris, 75015, France
HCL Lyon - CH Lyon Sud
Pierre-Bénite, 69495, France
Pôle Cardiovasculaire et Métabolique - Hôpital Larrey
Toulouse, 31059, France
CHRU de Tours
Tours, 37044, France
Related Publications (1)
Parker VER, Keppler-Noreuil KM, Faivre L, Luu M, Oden NL, De Silva L, Sapp JC, Andrews K, Bardou M, Chen KY, Darling TN, Gautier E, Goldspiel BR, Hadj-Rabia S, Harris J, Kounidas G, Kumar P, Lindhurst MJ, Loffroy R, Martin L, Phan A, Rother KI, Widemann BC, Wolters PL, Coubes C, Pinson L, Willems M, Vincent-Delorme C; PROMISE Working Group; Vabres P, Semple RK, Biesecker LG. Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum. Genet Med. 2019 May;21(5):1189-1198. doi: 10.1038/s41436-018-0297-9. Epub 2018 Oct 1.
PMID: 30270358RESULT
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 4, 2015
First Posted
May 14, 2015
Study Start
May 1, 2015
Primary Completion
November 1, 2016
Study Completion
November 1, 2016
Last Updated
November 21, 2025
Record last verified: 2025-11