Segmental overgrowth caused by somatic PI3K hyperactivation
Conditions
Interventions
Trade Name: Rapamune
Product Name: Sirolimus
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Sirolimus
CAS Number: CAS 53123-88
Sponsors
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
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
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) 16 132 OR a creatinine clearance or radioisotope GFR 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate if sirolimus is effective at reducing overgrowth in PIK3CA-related overgrowth, and to quantify its efficacy. To measure the effect size of sirolimus therapy in reducing pathological overgrowth in PIK3CA related overgrowth to enable statistical power calculations for a future randomised controlled trial (RCT) ; Secondary Objective: ? To establish optimal sirolimus dosing algorithms for a future RCT ? To establish if inter-patient comparison will be feasible in a future RCT ? To evaluate alternative treatment outcomes for inclusion as primary or secondary end-points in a future RCT ;Primary end point(s): To calculate an effect size of sirolimus therapy in the treatment of PIK3CA-related overgrowth;Timepoint(s) of evaluation of this end point: This will be evaluated at the end of the trial following completion of 6 months of sirolimus therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): I To establish optimal sirolimus dosing algorithms for a future RCT II To establish if inter-patient comparison will be feasible in a future RCT III To evaluate alternative treatment outcomes for inclusion as primary or secondary end-points in a future RCT ;Timepoint(s) of evaluation of this end point: This will be evaluated at the end of the trial following completion of 6 months of sirolimus therapy. | — |
Countries
United Kingdom, United States
Contacts
Public ContactCarrie Bayliss
CCTU
Outcome results
None listed