Sirolimus treatment for segmental overgrowth

Phase 1

• Conditions: Segmental overgrowth caused by somatic PI3K hyperactivation; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2014-000484-41-GB
• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-03-31
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 11

Inclusion Criteria

Have given, or their guardian has given written informed consent to participate
Aged: 3-65 years inclusive
Male or female
Post-zygotic PIK3CA mutation
Clinically stable in the opinion of the investigator
Measurably progressive overgrowth, in current progression or with clinical history of overgrowth progression
Have undergone an MRI and/or DXA scan in the previous 6 months as part of the Investigation of Segmental Overgrowth Disorders study
All women of childbearing potential and all sexually active male participants must agree to use effective contraception
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

The participant may not enter the study if ANY of the following apply:

•Aged 2 years or younger or aged 66 years or older
•Pregnant or breastfeeding
•Male and Female participants of childbearing potential who are not using an effective method of contraception (during treatment and up to 12 weeks after sirolimus discontinuation)
•Hypersensitivity to sirolimus or any of the excipients
•Any current medical disorder or medication likely to impair ability to follow the study protocol safely and effectively
•Incapacity to give informed consent
•Sirolimus treatment in the prior 4 weeks
•Personal history of malignancy or ongoing investigations for malignancy
•Active skin infections requiring antibiotics or anti-viral medication
•HCV/HBV/HIV seropositivity
•Previous/ active MTB infection
•Active Pneumonitis
•Inability to attend study visits
•If less than 3 months post-surgery
•Inadequate bone marrow function defined as:
- Peripheral absolute neutrophil count (ANC) < 1.0 x10^9/l
- Platelet count < 100 x10^9/l
- Haemoglobin <10.0 g/dL
•Inadequate renal function defined as:
A serum creatinine based on age as follows:
Age (years)Maximum Serum Creatinine (µmol/l)
= 570.4
6 11 >16132

OR a creatinine clearance or radioisotope GFR < 70ml/min/1.73 m2
•Inadequate liver function defined as:
- Bilirubin (sum of conjugated + unconjugated) > 1.5 x upper limit of normal
(ULN) for age, and
- SGPT (ALT) > 5 x upper limit of normal (ULN) for age, and
- Serum albumin > 30 g/dL.
•Inadequate Fasting LDL cholesterol > 4.2 mmol/l

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified