Overview

This trial is active, not recruiting.

Conditions tuberous sclerosis complex (tsc), lymphangioleiomyomatosis (lam)
Treatments everolimus (rad001), placebo
Phase phase 3
Sponsor Novartis Pharmaceuticals
Start date April 2009
End date June 2011
Trial size 118 participants
Trial identifier NCT00790400, 2008-002113-48, CRAD001M2302

Summary

This study will evaluate the safety and efficacy of RAD001 in treating patients with Angiomyolipoma associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Study drug was given by continuous oral daily dosing of two 5 mg tablets.
everolimus (rad001) RAD001
Everolimus is used in 5 mg strength tablets, blister-packed under aluminum foil in units of ten tablets and dosed on a daily basis. 10mg daily dosing throughout the trial.
(Placebo Comparator)
Placebo was given by continuous oral daily dosing of two 5 mg tablets. (Placebo arm closed when study was unblinded and all patients transitioned to everolimus.)
placebo
Matching placebo was provided as a matching tablet and was also blister-packed under aluminum foil in units of ten.

Primary Outcomes

Measure
Angiomyolipoma Response Rate as Per Central Radiology Review (Double-blind Period)
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 analysis cut-off date (30-June-2011).

Secondary Outcomes

Measure
Time to Angiomyolipoma Progression as Per Central Radiology Review (Double-blind Period)
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 analysis cut-off date (30-June-2011).
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 analysis cut-off date (30-June-2011).
Percentage of Participants With Renal Impairment
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 analysis cut-off date (30-June-2011).
Change From Baseline in Plasma Angiogenic Molecules
time frame: Baseline, 12 Months

Eligibility Criteria

Male or female participants at least 18 years old.

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 Non-interventional follow-up inclusion: - No angiomyolipoma progression at time of study treatment discontinuation and no plan to continue treating their angiomyolipoma(s) with systemic therapy - Non-interventional follow-up phase consent 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 Non-interventional follow-up phase exclusion: - Starting treatment with any mTOR inhibitor - Embolization immediately after discontinuing study treatment - Surgical resection of angiomyolipoma after discontinuing study treatment - Prior kidney CT/MRI already performed 1-year after discontinuation of everolimus Other protocol-defined inclusion/exclusion criteria may apply

Additional Information

Official 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)
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by Novartis.