Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00790400
• Date of registration: 10/11/2008
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM) EXIST-2
• Scientific title: A Randomized, Double-blind, Placebo-controlled Study of RAD0001 in the Treatment of Angiomyolipoma in Patients With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
• Date of first enrolment: April 2009
• Target sample size: 118
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00790400
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Canada, France, Germany, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, United Kingdom, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or Female 18 years or older

- Clinically definite diagnosis of Tuberous Sclerosis Complex according to the modified
Gomez criteria or sporadic LAM (biopsy-proven or compatible chest CT scan)

- Clinically definite diagnosis of renal angiomyolipoma

- At least one Angiomyolipoma of = 3 cm in its longest diameter using CT or MRI

- Females of child bearing potential must use birth control and have documentation of
negative pregnancy test

- Written informed consent according to local guidelines

Exclusion Criteria:

- Recent heart attack, cardiac related chest pain or stroke

- Severely impaired lung function

- Bleeding related to angiomyolipoma or embolization during 6 months prior to
randomization

- Clinically significant chylous ascites

- Clinically significant hematological or hepatic abnormality

- Severe liver dysfunction

- Severe kidney dysfunction

- Pregnancy or breast feeding

- Current infection

- History of organ transplant

- Surgery within two months prior to study enrollment

- Prior therapy with a medication in the same class as Everolimus

- Recent use of an investigational drug

- Bleeding diathesis or on oral anti-vitamin K medication

- Uncontrolled high cholesterol

- Uncontrolled diabetes

- HIV

- Inability to attend scheduled clinic visits

- Patients with metal implants thus prohibiting MRI evaluations

- Angiomyolipoma which requires surgery at the time of randomization

- History of malignancy

- Severe or uncontrolled medical conditions which would cause an unacceptable safety
risk or compromise compliance with the protocol



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lymphangioleiomyomatosis (LAM)

Tuberous Sclerosis Complex (TSC)

Intervention(s)

Drug: Everolimus Placebo

Drug: Everolimus (RAD001)

Primary Outcome(s)

Angiomyolipoma Response Rate as Per Central Radiology Review [Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years]

Secondary Outcome(s)

Change From Baseline in Plasma Angiogenic Molecules - Vascular Endothelial Growth Factor (VEGF) Marker [Time Frame: 4 weeks, 12 weeks, 24 weeks, 36 weeks 48 weeks, 60 weeks, 72 weeks]

Everolimus Blood Concentrations (C2h) at 2 Hours Post-dose [Time Frame: 2 hours post-dose administration at Weeks 2, 4, 12, 24, 48]

Time to Angiomyolipoma Progression as Per Central Radiology Review [Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years]

Time to Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response [Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years]

Duration of Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response [Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years]

Everolimus Trough Concentrations (Cmin) [Time Frame: Prior to dosing at weeks 2, 4, 12, 24, 48]

Percentage of Participants With Renal Impairment [Time Frame: Day 1 up to 28 days after end of treatment]

Skin Lesion Response Rate as Per Investigator (Only Patients With at Least One Skin Lesion at Baseline) [Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years]

Duration of Skin Lesion Response - Only Everolimus Patients With Best Overall Skin Lesion Response of Complete Clinical Response (CCR) or Partial Response (PR) [Time Frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years]

Secondary ID(s)

CRAD001M2302

2008-002113-48

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/08/2012
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00790400