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

Growth and Development Clinical Trial

— EXIST-LT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02338609
• Other study ID #: CRAD001M2305
• Secondary ID: 2013-003795-13
• Status: Completed
• Phase: Phase 4
• Start date: December 17, 2014
• Est. completion date: December 18, 2023

Study information

• Verified date: February 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 18, 2023
• Est. primary completion date: December 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Growth and Development

Intervention

Drug:
• Everolimus
Blood sample and Tanner Stage assessment
• Envirolimus drug class as prescribed by Physician
At the discretion of the investigator, patients may be treated with commercially available everolimus, as per local product information/ standard of care.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Brussel
Russian Federation	Novartis Investigative Site	Moscow
United States	Cinn Children Hosp Medical Center SC	Cincinnati	Ohio
United States	Texas Scottish Rite Hospital for Children SC	Dallas	Texas
United States	University Of California Los Angeles SC	Los Angeles	California
United States	Minnesota Epilepsy Group	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Neuropsychological development	TSC-Associated-Neuropsychiatric-Disorders (TAND) Checklist will be used to follow-up patient neuropsychological development	Annually up to 12 years
Secondary	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
Secondary	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