Clinical trial NCT02443818: Sirolimus Effect on Hypertrophic Syndromes Related Gene PIK3CA
Official title: Non-randomised Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Due to PIK3CA- Related Overgrowth
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Segmental Overgrowth Disorders Due to PIK3CA
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2015-05-14
Enrollment: 16
Sex: ALL
Minimum age (years): 3
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Detailed description: The duration of participation is 15 months:

* Visit screening: blood test, pre-clinical evaluation, urine collection and chest X-ray.
* First 6 months: participants will have their overgrowth monitored. This step includes 2 visits taking place at the University Hospital of Dijon: complete clinical evaluation, MRI of the body part by the overgrowth and Dual-energy X-ray absorptiometry (DXA).
* Next 6 months: participants will take Sirolimus. This step includes 2 visits (4 and 13 weeks after the start of treatment at local hospital): blood test, urine collection and clinical evaluation.

and 1 end of study visit after 6 months of treatment taking place at the University Hospital of Dijon: blood test, complete clinical evaluation, urine collection, MRI and DXA.

Participants will have several blood and urine tests between visits (1 and 2 weeks after the start of treatment at a local laboratory).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Inability to attend study visits

Primary outcomes:
measure: Measure of the relative percentage of the excess tissue volume evolution at the affected site by volumetric MRI.
timeFrame: Change from baseline at 6 and 12 months
Secondary outcomes:
measure: Measure sites of overgrowth by DXA, MRI and circumferential measurements
timeFrame: Change from baseline at 6 and 12 months
measure: To determine optimal sirolimus dosing algorithms by plasma assay
timeFrame: 12 months
measure: Number of hospitalisation and surgery
timeFrame: 12 months
measure: quality of life measured by a questionnaire in the pre- and post-treatment periods
timeFrame: At 6 and 12 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Bordeaux
country: France
facility: CHU de Bordeaux - GH Pellegrin
city: Dijon
country: France
facility: CHU de DIJON
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
city: Montpellier
country: France
facility: CHRU de Montpellier - Hôpital Saint-Eloi
city: Nancy
country: France
facility: Hopitaux de Brabois Chu Nancy
city: Nantes
country: France
facility: Hôpital mère-enfant de Nantes
city: Paris
country: France
facility: CHU Paris - Necker
city: Pierre-Bénite
country: France
facility: HCL Lyon - CH Lyon Sud
city: Toulouse
country: France
facility: Pôle Cardiovasculaire et Métabolique - Hôpital Larrey
city: Tours
country: France
facility: CHRU de Tours
Study officials:
References: