An open-label, multi-center, expanded access study of RAD001 in patients with subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC). The EFFECTS STUDY: Everolimus For Fast Expanded aCcess in TSC SEGA - EFFECTS STUDY

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2010-022583-13-CZ
• Date of registration: 23/02/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: An open-label, multi-center, expanded access study of RAD001 in patients with subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC). The EFFECTS STUDY: Everolimus For Fast Expanded aCcess in TSC SEGA - EFFECTS STUDY
• Scientific title: An open-label, multi-center, expanded access study of RAD001 in patients with subependymal giant cell astrocytomas (SEGA) associated with tuberous sclerosis complex (TSC). The EFFECTS STUDY: Everolimus For Fast Expanded aCcess in TSC SEGA - EFFECTS STUDY
• Date of first enrolment: 01/06/2011
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022583-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, France, Germany, Greece, Hungary, Italy, Spain

Contacts

• Name: Informacní služba-klin.hodnocení
• Affiliation: Novartis s.r.o.

• Name: Informacní služba-klin.hodnocení
• Affiliation: Novartis s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female of age 3 years or older
• Clinically definite diagnosis of tuberous sclerosis according to the modified Gomez criteria (Roach 1998, Hyman 2000, Table 5-1).
Clinically definite diagnosis is defined as either of the following:
• Two Major Features from Table 5-1.
• One Major Feature plus two Minor Features from Table 5-1.
• Presence of at least one SEGA lesion identified by MRI or CT (according to local requirements).
Note: SEGA lesions are only diagnosed in patients with TSC. They arise in the subependymal layer of the lateral ventricle and are usually located near the foramen of Monroe and enhance homogeneously with contrast on MRI with no evidence of surrounding edema.
• If female and of child-bearing potential, documentation of negative pregnancy test prior to enrollment. Sexually active female patients (and female partners of male patients) must use adequate contraceptive measures while on study and for up to 8 weeks after ending treatment.
• Written informed consent according to local guidelines
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• Patients for whom SEGA-related surgery is required and planned
• History of myocardial infarction, angina or stroke related to atherosclerosis
• Known impaired lung function (e.g. FEV1 or DLCO = 70% of predicted)
• Significant hematological or hepatic abnormality (i.e. transaminase levels > 2.5 x ULN or serum bilirubin > 1.5 x ULN, hemoglobin < 9 g/dL, platelets < 80,000/mm3, absolute neutrophil count < 1,000/mm3).
• Ongoing or active infection at date of enrollment
• Patients with Hepatitis B or C
• Prior history of organ transplantation
• Recent surgery (involving entry into a body cavity or requiring sutures) within one month prior to enrollment
• Use of an investigational drug within the 30 days prior to enrollment
• Uncontrolled hyperlipidemia: Fasting serum cholesterol > 300 mg/dL OR >7.75 mmol/L AND fasting triglycerides > 2.5 x ULN
• Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN
• Patients with bleeding diathesis or on oral anti-vitamin K medication
• Serum creatinine > 1.5 x ULN.
• Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks:
• 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).
• Patients with a known hypersensitivity to RAD001 or other rapamycin analogs (sirolimus, temsirolimus), or to its excipients
• For the purpose of MRI assessments (if applicable):
• Ferromagnetic metal implants other than those approved as safe for use in MR scanner (e.g., braces, some types of aneurysm clips, shrapnel)
• Patients suffering from uncontrollable claustrophobia or physically unable to fit into the machine (e.g. obesity)
• Patients with known history of HIV seropositivity
• Inability to attend scheduled clinic visits and noncompliance with scheduled clinic visits required for dose monitoring, dose adjustment and toxicity managment
Pregnant or nursing (lactating) women, where pregnancy is defined asthe state of a female fter conception and until the termination of gestation, confirmed by a positive hCG aboratory test.Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 56 days after stopping RAD001 medication. Highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
• Combination of any two of the following (a+b or a+c, or b+c): a. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have compar

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

Health Condition(s) or Problem(s) studied

The study will evaluate the safety of RAD001 in patients with subependymal giant cell astrocytomas (SEGA) associated with Tuberous Sclerosis Complex (TSC).

Intervention(s)

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

Primary Outcome(s)

Main Objective: To evaluate safety of RAD001 in patients with SEGA associated with TSC.

Primary end point(s): Safety:
Grade 3 and 4 Adverse Events, Serious Adverse Events

Secondary Objective: To evaluate the investigator’s best overall response rate of RAD001 in patients with SEGA associated with TSC.

Secondary ID(s)

2010-022583-13-DE

CRAD001MIC02

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 21/09/2019
• Date Completed: 11/03/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-022583-13/results