Long-term monitoring of growth and development of pediatric patients previously treated with everolimus

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2013-003795-13-BE
• Date of registration: 17/11/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Long-term monitoring of growth and development of pediatric patients previously treated with everolimus
• Scientific title: Long-term follow-up study to monitor the growth and development of pediatric patients previously treated with everolimus in study CRAD001M2301 - EXIST-LT
• Date of first enrolment: 10/12/2014
• Target sample size: 48
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003795-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: CRAD001MIC03 Study; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): yes

Countries of recruitment

Belgium, Canada, Poland, Russian Federation, United States

Contacts

• Name: Clinical Trial Information desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

Inclusion criteria:
1. Pediatric female patients who were on study treatment in study CRAD001M2301 within the past 3 months and have not reached Tanner Stage V or age 17 at the time of completion of study CRAD001M2301
or
2. Pediatric male patients who were on study treatment in study CRAD001M2301 within the past 3 months and have not reached Tanner Stage V or age 17 at the time of completion of study CRAD001M2301.
3. Written informed consent according to local guidelines.
Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Pediatric female patients who were on study treatment in study CRAD001M2301 and have not reached Tanner Stage V but are within 3 month of turning age 16
or
2. Pediatric male patients who were on study treatment in study CRAD001M2301 and have not reached Tanner Stage V but are within 3 months of turning age 17
3. Any patient who was pregnant prior to start of study CRAD001M2305


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Subependymal Giant Cell Astrocytoma (SEGA) associated with Tuberous Sclerosis Complex (TSC)
MedDRA version: 21.0 Level: LLT Classification code 10045138 Term: Tuberous sclerosis System Organ Class: 100000004850

Intervention(s)

Trade Name: Votubia
Product Name: everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Trade Name: Votubia
Product Name: everolimus
Product Code: RAD001
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Votubia
Product Name: everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: Votubia
Product Name: everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Votubia
Product Name: everolimus
Product Code: RAD001
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-

Trade Name: Votubia
Product Name: everolimus
Product Code: RAD001
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)

Primary Outcome(s)

Primary end point(s): Percentage of patients who achieved Tanner Stage V at or before age of 16 (females) or 17 (males).
Height standard deviation score by year
Mean endocrine laboratory values (FSH, LH, and estrogen or testosterone) by age

Main Objective: To monitor the growth and development of pediatric patients with TSC-associated SEGA, previously enrolled in Study CRAD001M2301, who had received everolimus as part of study CRAD001M2301 and may or may not be continuing treatment with everolimus.

Timepoint(s) of evaluation of this end point: Annually

Secondary Objective: ? Long-term safety
? Age at menarche (females)
? Age at thelarche (females)
? Age at adrenarche (males)
? Age at Tanner Stages II-V
? Assess neuropsychological development by TAND Checklist
? Compare CRAD001M2305 and CRAD001MIC03 on height, BMI and
sexual development (using Tanner Stages)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Annually except for adverse events, concomitant medication and appearance of menarche, which will be monitored every 3 months

Secondary end point(s): Age at start of menses (menarche) – for females
Age at onset of breast development (thelarche) – for females
Age at pubic hair development (adrenarche) – for males
Age at Tanner Stage II-V - all patients
TAND Checklist individual responses over time since the enrollment date
Indirect comparison between CRAD001M2305 and CRAD001MIC03 will be performed on the following endpoints:
Percentage of patients who achieved Tanner Stage V at or before age of 16 (females) or 17 (males).
Height/BMI standard deviation score by year since baseline.


Safety will be assessed by the National Cancer Institute’s (NCI) Common Toxicity
Criteria for Adverse Events (CTCAE), version 3.0
Notes:
? Safety assessments will consist of monitoring and recording adverse and serious
adverse events
? Safety follow-up as per product information

Secondary ID(s)

CRAD001M2305

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 03/12/2014
Contact: