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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02338609

Collaborator

(none)

Enrollment

Locations

Arms

141.3

Anticipated Duration (Months)

2.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Growth and Development	Drug: Everolimus Drug: Envirolimus drug class as prescribed by Physician	Phase 4

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Dec 17, 2014

Anticipated Primary Completion Date :

Jun 8, 2026

Anticipated Study Completion Date :

Sep 25, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Everolimus 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 Blood sample and Tanner Stage assessment
Experimental: Physician Choice	Drug: 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.

Arm

Intervention/Treatment

Experimental: Everolimus

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

Blood sample and Tanner Stage assessment

Experimental: Physician Choice

Drug: 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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Long-term safety as assessed by National Cancer Institute (NCI) Common Toxicity Criteria or Adverse Events (CTCAE) [Annually up to 12 years]
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.
Age at menarche/thelarche (females) or adrenarche (males) [Annually up to 12 years]
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
Age at Tanner Stage II, III, IV, V [Annually up to 12 years]
Age at when each Tanner Stage is achieved will be collected and compared against known standards.
Neuropsychological development [Annually up to 12 years]
TSC-Associated-Neuropsychiatric-Disorders (TAND) Checklist will be used to follow-up patient neuropsychological development
Height/BMI standard deviation score by year since baseline [Annually up to 12 years]
Height, weight, Tanner staging will be compared to data from TSC patients who have not been treated with everolimus
Percentage of patients who achieved Tanner Stage V at or before age 16 (females) or 17 (males) [Annually up to 12 years]
Patients will be assessed annually until Tanner Stage 5 is achieved

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Years to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at Los Angeles SC	Los Angeles	California	United States	90095
2	Minnesota Epilepsy Group	Saint Paul	Minnesota	United States	55102
3	Cincinnati Children s Hospital Medical Center SC	Cincinnati	Ohio	United States	45229-3039
4	Texas Scottish Rite Hospital for Children SC	Dallas	Texas	United States	75219
5	Novartis Investigative Site	Brussel		Belgium	1090
6	Novartis Investigative Site	Moscow		Russian Federation	127412