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: 5 August 2014
• Main ID: EUCTR2010-022583-13-DE
• Date of registration: 23/12/2010
• 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
• 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:

Countries of recruitment

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

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 pre-menopausal 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
• Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
If barrier contraceptives are used, they must be continued throughout the study by both sexes


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: RAD001 2,5 mg
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)

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

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

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

Secondary ID(s)

CRAD001MIC02