Expanded access study of RAD001 in patient with angiomyolipoma associated with tuberous sclerosis complex (TSC)

• Register: EUCTR
• Last refreshed on: 27 October 2014
• Main ID: EUCTR2012-005397-63-ES
• Date of registration: 16/01/2014
• Prospective Registration: No
• Primary sponsor: Novartis Farmacéutica, S.A,
• Public title: Expanded access study of RAD001 in patient with angiomyolipoma associated with tuberous sclerosis complex (TSC)
• Scientific title: An open-label, multi-center, expanded access study of RAD001 in patients with angiomyolipoma associated with tuberous sclerosis complex (TSC)
• Date of first enrolment: 19/04/2013
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005397-63
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no 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: no

Countries of recruitment

Spain

Contacts

• Name: Departamento Médico de Oncología
• Affiliation: Novartis Farmacéutica, S.A

• Name: Departamento Médico de Oncología
• Affiliation: Novartis Farmacéutica, S.A

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female ? 18 years of age.
2. Clinically definite diagnosis of tuberous sclerosis according to the modified Gomez criteria (Roach 1998, Hyman 2000, Table 5-1). Clinically definite diagnosis of tuberous sclerosis according to the modified Gomez criteria 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. Clinically definite diagnosis of renal angiomyolipoma (according to local requirements)
4. Presence of at least one angiomyolipoma ? 3 cm in its longest diameter using CT/MRI. The choice of 3 cm reflects the vague limits between a justified wait and watch policy and the more proactive surgical intervention approaches.
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, while on study and for 8 weeks after ending treatment.
6. Written informed consent prior to any screening procedures according to local guidelines.
Are the trial subjects under 18? no
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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Patients with angiomyolipoma which, in the opinion of the investigator, requires surgery at the time of study inclusion
2. Angiomyolipoma-related bleeding or embolization during the 6 months prior to study inclusion
3. History of myocardial infarction, angina or stroke related to atherosclerosis.
4. Known impaired lung function (e.g. FEV1 or DLco ? 70% of predicted)
5. Significant hematological or hepatic abnormality (i.e., transaminase levels > 2.5 × upper limit of normal (ULN), serum bilirubin > 1.5 × ULN, hemoglobin < 9g/dL, platelets < 80,000/mm3, or absolute neutrophil count < 1,000/mm3).
6. Ongoing or active infection at the date of enrollment
7. Patients with a known history of HIV seropositivity.
8. Prior history of organ transplantation.
9. Recent surgery (involving entry into a body cavity or requiring sutures) within the 2 months prior to study inclusion.
10. Patient with a known hypersensitivity to RAD001 or other rapamycin analogs (sirolimus temsirolimus), or its excipients
11. Use of an investigational drug within the 30 days prior to study inclusion
12. Uncontrolled hyperlipidemia: Fasting serum cholesterol > 300 mg/dL (or > 7.75 mmol/L), AND fasting triglycerides > 2.5 × ULN.
13. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 × ULN.
14. Patients with bleeding diathesis or on oral anti-vitamin K medication (except low dose warfarin).
15. Serum creatinine > 1.5 x ULN
16. Any severe and/or uncontrolled medical conditions which could cause unacceptable safety risks:
a. uncontrolled hypercholesterolemia/hypertriglyceridemia

b. 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).
17. For the purpose of MRI assessments:
a. Ferromagnetic metal implants other than those approved as safe for use in MR scanner (e.g., braces, some types of aneurysm clips, shrapnel)
b. Patients suffering from uncontrollable claustrophobia or physically unable to fit into the machine (e.g., obesity, etc).
Note: patients with vagal nerve stimulators are permitted to have CT assessments of angiomyolipoma unless local or national regulations do not permit this.
18. Inability to attend scheduled clinic visits and noncompliace with scheduled clinic visits required for toxicity management
19. Female patients who are pregnant or breast feeding, women of child-bearing potential, unless they are using effective methods of contraception during the study and for 8 weeks after ending treatment and sexually active males unless they use a condom during the study and for 8 weeks after the end of treatment.

20. Prior randomization to either arm of study CRAD001M2302


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]

Angiomyolipoma associated with either Tuberous Sclerosis Complex (TSC)
MedDRA version: 16.1 Level: PT Classification code 10051810 Term: Angiomyolipoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Votubia
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: 5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Until the drug becomes commercially available for angiomyolipoma associated to TSC in Spain or up to 1 year after FPFV , whichever occurs first.

Secondary Objective: To evaluate the angiomyolipoma response rate on RAD001
to evaluate safety of RAD001 in patients with angiomyolipoma associated with TSC

Primary end point(s): Grade 3 and Grade 4, Serious Adverse Events, and AEs that cause a change in study drug dosing. Frequency of laboratory values (hematology / chemistry) that are new or worsening based on the common toxicity criteria grade (NCI-CTCAE v. 4.03)

Main Objective: To evaluate the dose-limiting safety of everolimus in patients with angiomyolipoma associated with TSC.

Secondary Outcome(s)

Secondary end point(s): To evaluate Angiomyolipomas volume changes during the trial by CT scan /MRI from baseline visit
Adverse Events and Serious Adverses Events of any grade

Timepoint(s) of evaluation of this end point: Until the drug becomes commercially available for angiomyolipoma associated to TSC in Spain or up to 1 year after FPFV , whichever occurs first.

Secondary ID(s)

CRAD001MES12

Source(s) of Monetary Support

Novartis Farmacéutica,S.A