Sirolimus Effect on Hypertrophic Syndromes Related Gene PIK3CA

Segmental Overgrowth Disorders Due to PIK3CA Clinical Trial

— PROMISE  

Official title:

Non-randomised Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Due to PIK3CA- Related Overgrowth

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02443818
• Other study ID #: OLIVIER-FAIVRE Sirolimus
• Status: Completed
• Phase: Phase 2
• Start date: May 2015
• Est. completion date: November 2016

Study information

• Verified date: October 2018
• Source: Centre Hospitalier Universitaire Dijon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Segmental Overgrowth Disorders Due to PIK3CA

Intervention

Drug:
• Sirolimus
Low dose sirolimus will be given in daily dosing to achieve trough levels of 2-6 ng/ ml.

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CHU de Bordeaux - GH Pellegrin	Bordeaux
France	CHU de DIJON	Dijon
France	Hôpital Jeanne de Flandre	Lille
France	CHRU de Montpellier - Hôpital Saint-Eloi	Montpellier
France	Hopitaux de Brabois Chu Nancy	Nancy
France	Hôpital mère-enfant de Nantes	Nantes
France	CHU Paris - Necker	Paris
France	HCL Lyon - CH Lyon Sud	Pierre-Bénite
France	Pôle Cardiovasculaire et Métabolique - Hôpital Larrey	Toulouse
France	CHRU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Dijon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Measure sites of overgrowth by DXA, MRI and circumferential measurements		Change from baseline at 6 and 12 months
Secondary	To determine optimal sirolimus dosing algorithms by plasma assay		12 months
Secondary	Number of hospitalisation and surgery		12 months
Secondary	quality of life measured by a questionnaire in the pre- and post-treatment periods	The WHO-QOL-BREF questionnaire will be used for adults. For children, PedsQL™ questionnaire for children and parents report for children questionnaires will be used	At 6 and 12 months