Segmental overgrowth syndrome
Conditions
Interventions
Trade Name: Rapamune® 1 mg/ml
Lösung zum Einnehmen
Product Name: Rapamune® 1 mg/ml
Pharmaceutical Form: Concentrate for oral solution
INN or Proposed INN: SIROLIMUS
CAS Number: 53123-88-9
Concentratio
Sponsors
Medical Center - University of Freiburg
Medical Center - University of Freiburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged = 3 years (no upper limit) 2. Signed written informed consent (patient = 18 years or person(s) having the care and custody of the patient 9 g/dL). 7. Negative urine pregnancy test in females with a childbearing potential. 8. If female and of child-bearing potential, documentation of negative pregnancy test prior to enrollment. Sexually active female patients, male patients and female partners of male patients must use adequate contraceptive measures while on study and for up to 12 weeks after ending treatment. Are the trial subjects under 18? yes Number of subjects for this age range: 18 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any concurrent therapy with chemotherapy agents or biologic agents or other immunosuppressive therapy or radiation therapy. 2. Patients who have received live vaccines in the past 30 days prior to informed consent. 3. Patients on medication with CYP3A4 inhibitors/inducers which are not replaced by other equivalent medications for the study period. 4. Patients who have known immunodeficiency or HIV seropositivity. 5. Patients with known history of prior and/or ongoing malignancy within the last 5 years. 6. Patients with known interstitial lung disease, pneumonitis or with bleeding diathesis. 7. Patients with prior use of sirolimus or other mTOR inhibitors or any analogue within the last 6 months 8. Any planned surgery within study period related to overgrowth lesions. 9. Pre-existing chronic wounds. 10. Triglycerides > 400 mg/dL (> 4.5 mmol/L) or total cholesterol > 300 mg/dl (> 7.8 mmol/L). 11. Creatinine clearance = 60 ml/min (Cockcroft-Gault formula). 12. Proteinuria = 30 mg/dl on dipstick and 24 hours proteinuria > 0.8 g/24 hours. 13. Intake of St John’s Wort and/or grapefruit and grapefruit juice. 14. Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks such as: • Uncontrolled hypercholesterolemia/ hypertriglyceridemia • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome). 15. Patients with a known hypersensitivity to sirolimus or other mTOR inhibitors or any analogs or to its excipients. 16. Patients unwilling to or unable to comply with the planned therapeutic regimen or to comply with the study treatment visits including blood sample collection within the protocol. 17. Female patients who are pregnant or breast feeding, or patients of reproductive potential who are not using effective birth control methods (see: inclusion criteria). If barrier contraceptives are used, they must be continued throughout the study by both sexes. 18. Patients must abstain from donating blood, semen, or sperm during participation in the study until 3 months after the end of participation in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of sirolimus to reduce the size of defined target lesions in patients with segmental overgrowth syndromes.;Secondary Objective: To evaluate changes in disfigurement assessed by serial digital photograph To evaluate changes in health-related Quality of Life To evaluate changes in pain To evaluate changes in neuropsychological testing compared to baseline values. To evaluate changes in biomarkers compared to respective baseline values. To assess the inhibition of the mTOR pathway. Assessment of safety. Study drug compliance. ;Primary end point(s): Best response: Complete Remission (CR), or Partial Remission (PR) until 6 months after start of therapy period (baseline) measured by MRI according to response criteria;Timepoint(s) of evaluation of this end point: until 6 months after baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Morphological changes in disfigurement compared to baseline by using a scale for external validation documented by photography after 3, 6 and 9 months of therapy Changes in Quality of life after 3, 6 and 9 months of therapy compared to baseline (for patients = 4 and = 17 years of age by KINDL® parents and Kiddy-KINDL® Kids 4-6 years, Kid-KINDL® Kids 7-13 years, Kiddo-KINDL® Teenager 14-17 years, and for patients = 18 by WHOQOL-BREF as well as Lansky (<16 years)/Karnofsky scale) Changes in pain after 3, 6 and 9 months of therapy compared to baseline by visual pain scales for adults and children Changes in neuropsychological tests (using Strengths and Difficulties Questionnaire (SDQ) Kids (6-11 years), Parents and Erwachsene = 18 years after 3, 6 and 6 9 months of therapy compared to baseline. Changes in IGFBP-3, IGF-1, VEGF compared to baseline values after 3, 6 and 6 9 months of therapyafter start of study treatment (baseline). Inhibition of mTOR in PBMCs assessed by immunoblotting after 3, 6 and 9 months after start of study treatment (baseline). Safety will be determined by observation of any adverse or serious adverse events. Evaluations will include clinical and laboratory assessments performed at the time points described in the flow chart. Criteria for assessment of safety will be based on standard criteria for monitoring, assessing, and reporting of adverse events (CTCAE criteria v. 5.0). Study drug compliance measured with patient diary. ;Timepoint(s) of evaluation of this end point: CR or PR after 6 months Changes in Quality of life after 3, 6 and 9 months. Changes in pain after 3, 6 and 9 months. Changes in neuropsychological tests after 3, 6 and 9 months. Morphological changes after 3, 6 and 9 months. Changes in IGFBP-3, IGF, VEGF after 3, 6 and 9 months. Inhibition of mTOR in PBMCs after after 3, 6 and 9 months. | — |
Countries
Germany
Contacts
Public ContactCo-ordinating Investigator
Medical Center – University of Freiburg, Center for Pediatrics
Outcome results
None listed