Sirolimus Effect on Hypertrophic Syndromes Related Gene PIK3CA (PROMISE)

University Hospital Center (CHU) Dijon Bourgogne

Status and phase

Completed

Phase 2

Conditions

Segmental Overgrowth Disorders Due to PIK3CA

Treatments

Drug: Sirolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT02443818

OLIVIER-FAIVRE Sirolimus

Details and patient eligibility

About

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).

Full 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).

Enrollment

16 patients

Sex

All

Ages

3 to 65 years old

Volunteers

No Healthy Volunteers

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