Long-term Follow-up for Growth and Development of Pediatric Patients From CRAD001M2301

Study Overview
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Brief Summary
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The primary objective of CRAD001M2305 is to report the long-term effects of everolimus treatment on height, weight and sexual development (using Tanner Stages) in children and adolescents with Tuberous Sclerosis Complex (TSC)-associated with Subependymal Giant Cell Astrocytoma (SEGA). The study will monitor the growth and development of pediatric patients with TSC-associated SEGA, previously enrolled in CRAD001M2301 until they reach Tanner Stage V, or until age 16 for females or 17 for males whichever occurs first.

Detailed Description
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CRAD001M2305 is a prospective, multi-center phase IIIb/IV study. This study will investigate if the physical and sexual development of pediatric patients is affected by previous or ongoing treatment with everolimus. The study will monitor the growth and development of pediatric patients with TSC-associated SEGA, previously enrolled in CRAD001M2301 until they reach Tanner Stage V, or until age 16 for females or 17 for males whichever occurs first. Continued treatment with everolimus is at investigator discretion and is not required for participation in CRAD001M2305. Growth (height, weight), and sexual development (Tanner Stages, sex hormone levels, age at menarche, thelarche (females) and adrenarche (males)), and brain development (assessed by TAND Checklist, dates of brain MRI) of patients participating in this long-term follow-up study will be followed at annual visits to the site until patients achieve Tanner Stage V or age 16 (females), age 17 (males) whichever occurs first. Adverse events, concomitant medication, appearance of menarche, will be monitored and data collected every 3 months (3-monthly). Unless clinically indicated these 3-monthly visits can be performed per telephone.

Official Title
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Long-term Follow-up Study to Monitor the Growth and Development of Pediatric Patients Previously Treated With Everolimus in Study CRAD001M2301

Conditions
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Growth and Development

Intervention / Treatment
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* Drug: Everolimus
* Drug: Envirolimus drug class as prescribed by Physician


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric female patients who were on study treatment in study [CRAD001M2301] within the past 63 months and have not reached Tanner Stage V or age 16 at the time of completion of [CRAD001M2301] or Pediatric male patients who were on study treatment in study [CRAD001M2301] within the past 6 months and have not reached Tanner Stage V or age 17 at the time of completion of [CRAD001M2301] Written informed consent according to local guidelines Exclusion Criteria: Pediatric female patients who were on study treatment in CRAD001M2301 and have not reached Tanner Stage V but are within 3 month of turning age 16 or Pediatric male patients who were on study treatment in CRAD001M2301 and have not reached Tanner Stage V but are within 3 months of turning age 17 Any patient who was pregnant prior to start of CRAD001M2305 Other protocol-defined Inclusion/Exclusion criteria

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus<br>All patients will have been previously treated with everolimus as part of CRAD001M2301. Continued treatment with everolimus is allowed but not required for participation in this study. However, the physician may choose to place the patient on another treatment. | Drug: Everolimus<br>* Blood sample and Tanner Stage assessment<br>|
| Experimental: Physician Choice<br> | Drug: Envirolimus drug class as prescribed by Physician<br>* At the discretion of the investigator, patients may be treated with commercially available everolimus, as per local product information/ standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who achieved Tanner Stage V at or before age 16 (females) or 17 (males) | Patients will be assessed annually until Tanner Stage 5 is achieved | Annually up to 12 years | 
| Height/Body Mass Index (BMI) standard deviation score since baseline | Height and weight (for BMI) will be assessed to monitor growth. | Annually up to 12 years | 
| Mean Endocrine laboratory values | Blood sample will be drawn to assess FSH, LH, testosterone (male) or estrogen (female) by age | Annually up to 12 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term safety as assessed by National Cancer Institute (NCI) Common Toxicity Criteria or Adverse Events (CTCAE) | Safety as assessed by National Cancer Institute (NCI) Common Toxicity Criteria or Adverse Events (CTCAE). Adverse Events (AEs)/Serious Adverse Events (SAEs), concomitant medications (conmeds) will be collected as needed. | Annually up to 12 years | 
| Age at menarche/thelarche (females) or adrenarche (males) | Age when patient achieve each benchmark will be recorded and compared with standards. Menarche = start of menses Thelarche = onset of breast development Adrenarche = pubic haor development | Annually up to 12 years | 
| Age at Tanner Stage II, III, IV, V | Age at when each Tanner Stage is achieved will be collected and compared against known standards. | Annually up to 12 years | 
| Neuropsychological development | TSC-Associated-Neuropsychiatric-Disorders (TAND) Checklist will be used to follow-up patient neuropsychological development | Annually up to 12 years | 
| Height/BMI standard deviation score by year since baseline | Height, weight, Tanner staging will be compared to data from TSC patients who have not been treated with everolimus | Annually up to 12 years | 
| Percentage of patients who achieved Tanner Stage V at or before age 16 (females) or 17 (males) | Patients will be assessed annually until Tanner Stage 5 is achieved | Annually up to 12 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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height,, TSC-associated SEGA,, weight,, Tanner Stage,, growth development,, everolimus,, RAD001