Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
- Conditions
- Angiomyolipoma in patients with either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)MedDRA version: 16.1Level: PTClassification code 10051810Term: AngiomyolipomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2008-002113-48-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 118
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) or sporadic LAM (biopsy-proven or compatible chest CT scan).
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 highly effective contraceptive measures, while on study and for 8 weeks after ending treatment.
6. Written informed consent according to local guidelines.
Non-interventional follow-up phase:
1. No angiomyolipoma progression at time of study treatment discontinuation and no plan to continue treating their angiomyolipoma(s) with systemic therapy
2. Non-interventional follow-up phase consent
Other protocol-defined inclusion criteria may apply.
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 118
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0
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)
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 MRI 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).
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
Non-interventional follow-up phase:
1. Starting treatment with any mTOR inhibitor
2. Embolization immediately after discontinuing study treatment
3. Surgical resection of angiomyolipoma after discontinuing study treatment
4. Prior kidney CT/MRI already performed 1-year after discontinuation of everolimus
Other protocol-defined exclusion criteria may apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method