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)
Conditions
Interventions
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 u
Sponsors
Novartis Farmacéutica, S.A,
Eligibility
Sex/Gender
All
Inclusion 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
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the dose-limiting safety of everolimus in patients with angiomyolipoma associated with TSC.;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);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
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
Spain
Contacts
Public ContactDepartamento Médico de Oncología
Novartis Farmacéutica, S.A
Outcome results
None listed