A randomized double-blind, placebo-controlled study of RAD001 in the treatment of Angiomyolipoma in patients with either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
- Conditions
- Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM).10027656
- Registration Number
- NL-OMON37228
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 21
1. Male or female * 18 years of 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) ) or sporadic LAM (biopsy-proven or compatible chest
CT scan). Clinically definite diagnosis of tuberous sclerosis according to the
modified Gomez criteria 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.
3. Clinically definite diagnosis of renal angiomyolipoma.
4. Presence of at least one angiomyolipoma * 3 cm in its longest diameter
using CT or MRI.
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 according to local guidelines.
1. Patients with angiomyolipomas which, in the opinion of the investigator, requires surgery at the time of randomization.
2. Angiomyolipoma-related bleeding or embolization during the 6 months prior to randomization.
3. History of myocardial infarction, angina or stroke related to atherosclerosis.
4. Impaired lung function, defined as any of the following:
For patients without lymphangioleiomyomatosis (LAM)
Known impaired lung function (e.g. FEV1 or DLco * 70% of predicted)
Note: pulmonary function testing at baseline is not required for patients
without LAM
For patients with lymphangioleiomyomatosis (LAM)
* DLCO *<35%, or
* O2 saturations below normal at rest, or
* O2 saturation *<88% on 6 minute walking test with up to 6 liter O2/minute
nasal oxygen
5. Chylous ascites sufficient to affect diaphragmatic function or pulmonary function testing.
6. Significant hematological or hepatic abnormality (i.e., transaminase levels > 2.5 × the upper limit of normal (ULN), serum bilirubin > 1.5 × ULN, hemoglobin < 9g/dL, platelets < 80,000/mm3, or absolute neutrophil count (ANC) < 1,000/mm3).
7. Pregnancy or breast feeding.
8. Intercurrent infection at date of randomization.
9. Prior history of organ transplantation.
10. Recent surgery (involving entry into a body cavity or requiring sutures) within the 2 months prior to randomization.
11. Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus).
12. Use of an investigational drug within the 30 days prior to randomization.
13. Uncontrolled hyperlipidemia: Fasting serum cholesterol > 300 mg/dL (or >7.75 mmol/L ) AND fasting triglycerides > 2.5 × ULN.
14. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 1.5 × ULN.
15. Patients with bleeding diathesis or on oral anti-vitamin K medication (except low dose warfarin).
16. Patients with a known history of HIV seropositivity.
17. Inability to attend scheduled clinic visits.
18. For the purpose of MRI assessments:
* 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, etc).
NOTE: patients with vagal nerve stimulators are permitted to have CT assessments of angiomyolipoma unless local or national regulations do not permit this.
19. Serum creatinine > 1.5 × ULN.
20. History of malignancy in the past two years, other than squamous or basal cell skin cancer.
21. Any severe and/or uncontrolled medical conditions which could cause
unacceptable safety risks or compromise compliance with the protocol, such
as:
1. * Grade 3 hypercholesterolemia/hypertriglyceridemia or * Grade 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment if given)
2. 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).
3. Active skin, mucosa, ocular or GI disorders of Grade > 1
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Objective:<br /><br>To compare the angiomyolipoma response rate on RAD001 versus placebo in<br /><br>patients with angiomyolipoma, associated with either TSC or LAM.</p><br>
- Secondary Outcome Measures
Name Time Method