A randomized, double-blind, placebo-controlled study of RAD001 in the treatment of patients with subependymal giant cell astrocytomas (SEGA) associated with Tuberous Sclerosis Complex (TSC) - N/A

• Conditions: This study will evaluate the antitumor activity of RAD001 versus placebo in patientswith subependymal giant cell astrocytomas (SEGA) associated with TuberousSclerosis Complex (TSC).

• Registration Number: EUCTR2007-006997-27-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-20
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

1. Male or female of any age.
2. Clinically definite diagnosis of tuberous sclerosis according to the modified
Gomez criteria (Roach et al, 1998; Hyman and Whittemore, 2000, Table 5-1).
Clinically definite diagnosis is defined as either of the following:
a. Two Major Features from Table 5-1.
b. One Major Feature plus two Minor Features from Table 5-1.
3. Presence of at least one SEGA lesion = 1.0 cm in its longest diameter using
MRI.
Note: SEGA lesions are only diagnosed in patients with TSC. They arise in the
subependymal layer of the lateral ventricle and are always located near the
foramen of Monro and enhance homogeneously with contrast on MRI with no
evidence of surrounding edema.
4. A recent MRI of the brain completed within 3 weeks (21 days) prior to the
patient’s randomization must be compared with an MRI of the brain performed at
an earlier stage of patient care (pre-baseline) and should demonstrate at least one of the following:
a. Serial growth, defined as at least a 25% increase in SEGA volume, or
b. Presence of a new SEGA lesion = 1 cm in its longest diameter, or
c. New or worsening hydrocephalus defined by assessment of ventricular
configuration changes, ventricular cap signs (periventricular edema) and
qualitative assessment of CSF flow dynamics.
Notes:
If a previous MRI is not available, a comparative review of two previous CT scans is
also acceptable to establish any of the above mentioned three conditions. In this
case, baseline/screening MRI should still be performed.
If only one prior CT scan was available, a second CT scan should be obtained to
allow like to like comparison of cranial images. Again, the baseline MRI should still
be performed. CT scans should be digitized and sent to the central reviewer for
confirmation of eligibility.
If the pre-baseline MRI or CT was only available on film (non-digital format) or
software for volumetric assessment was not available at the local site, the local
radiologist should make a qualitative assessment of the above-mentioned three
criteria. The non-digital MRI or CT must also be sent to Central Radiology for
review.
5. 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,
excluding estrogen containing contraceptives, while on study.
6. Written informed consent. Parents or legal guardians must sign the informed
consent for patients under 18 years old and for patients with developmental
delays. In addition, all minors aged 7 through 14 must sign an assent form, while
minors aged 15 up to 17 must sign an assent line on the Informed Consent Form
that will be signed by the parents or the legal guardians.
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

1. Patients for whom SEGA related surgery is likely to be required, in the opinion of
the investigator.
2. Prior brain surgery.
3. History of myocardial infarction, angina or stroke related to atherosclerosis
4. Impaired lung function, defined as any of the following:
a. FEV1 = 70% of predicted, or
b. DLCO = 70% of predicted, or
c. = 88% O2 saturation at rest in room air, or
d. for patients unable to perform pulmonary function testing:
i. clinical evidence of significantly impaired lung function, or
ii. radiological evidence of significant lung disease other than LAM
Note: Patients unable to perform a pulmonary function test (e.g. younger children,
patients with developmental delay) will have a baseline chest CT scan performed
5. 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).
6. Pregnancy or breast feeding.
7. Intercurrent infection at date of randomization.
8. Prior history of organ transplant.
9. Recent surgery (involving entry into a body cavity or requiring sutures) within the
2 months prior to randomization.
10. Prior therapy with mTOR inhibitors (e.g.sirolimus, temsirolimus, everolimus).
11. Use of an investigational drug within the 30 days prior to randomization.
12. Uncontrolled hyperlipidemia: Fasting serum cholesterol > 300 mg/dL OR > 7.75
mmol/L AND Fasting triglycerides > 2.5 x ULN.
13. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 x ULN.
14. Patients with bleeding diathesis or on oral anti-vitamin K medication (except low
dose warfarin).
15. Patients with known history of HIV seropositivity.
16. Inability to attend scheduled clinic visits.
17. For the purpose of MRI assessments:
a. Ferromagnetic metal implants (e.g., braces, some types of aneurysm clips,
shrapnel) unless approved as safe for use in MR scanner
b. Patients suffering from uncontrollable claustrophobia or physically unable to fit
into the machine (e.g., obesity, etc).
18. Serum creatinine > 1.5 x ULN.
19. History of malignancy in the past two years, other than squamous or basal cell
skin cancer.
20. Use of estrogen containing medications.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified