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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)

Primary Purpose

Tuberous Sclerosis Complex (TSC), Lymphangioleiomyomatosis (LAM)

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Everolimus (RAD001)
Everolimus Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tuberous Sclerosis Complex (TSC) focused on measuring Angiomyolipoma, AML, Tuberous Sclerosis Complex, TSC, mTOR, RAD001, Mammalian Target of Rapamycin, Everolimus, Afinitor, SEGA, Subependymal Giant Cell Astrocytoma, Seizures, Tuberous sclerosis complex (TSC), Tuberous sclerosis, benign tumors of brain, kidney, heart, eyes, lungs, skinTSC1, TSC2, hamaratin, tuberin, tumor growth suppressors, gyri, tubers, Sporadic Lymphangioleiomyomatosis., Lymphangioleiomyomatosis (LAM), rare lung disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • Barrow Tuberous Sclerosis Center
  • Massachusetts General Hospital Massachussetts General Hospita
  • Minnesota Epilepsy Group
  • Cincinnati Children's Hospital Medical Center
  • LeBonheur Childrens Medical Group SC-2
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Everolimus

Placebo

Arm Description

Study drug was given by continuous oral daily dosing of two 5 mg tablets.

Placebo was given by continuous oral daily dosing of two 5 mg tablets.

Outcomes

Primary Outcome Measures

Angiomyolipoma Response Rate as Per Central Radiology Review
Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume > 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2. For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.

Secondary Outcome Measures

Time to Angiomyolipoma Progression as Per Central Radiology Review
Time to angiomyolipoma progression (TTAP) is defined as time from date of randomization to date of first documented angiomyolipoma progression. Angiomyolipoma progression was defined as one or more of the following: Increase from nadir of ≥ 25% in angiomyolipoma volume to value greater than baseline; the appearance of a new angiomyolipoma ≥ 1.0 cm in longest diameter; an increase from nadir of 20% or more in the volume of either kidney to a value greater than baseline; angiomyolipoma-related bleeding grade ≥ 2. For the everolimus (core/extension periods) treatment group, the time to angiomyolipoma progression is defined starting from the start of everolimus. The baseline means the latest value on or before starting everolimus.
Skin Lesion Response Rate as Per Investigator (Only Patients With at Least One Skin Lesion at Baseline)
Skin lesion response rate in the double-blind period was determined only among patients with at least one skin lesion at baseline, and is the percentage of this group of patients with a best overall skin lesion response on the Physician's Global Assessment of Clinical Condition (PGA) of either complete clinical response (CCR) or partial response (PR). A complete clinical response (CCR) requires a grading of 0 indicating the absence of disease (histological confirmation is not required). Grades 1, 2, and 3 constitute partial response, indicating improvement of at least 50 percent, but less than 100 percent improvement. For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.
Percentage of Participants With Renal Impairment
Renal Impairment was measured by glomerular filtration rate which was calculated using the Modification of Diet in Renal Disease formula. Percentage of participants with renal impairment was reported. Severe renal impairment was defined as a GFR of <30ml/min/1.73m2.
Change From Baseline in Plasma Angiogenic Molecules - Vascular Endothelial Growth Factor (VEGF) Marker
Blood samples for biomarker assessment were collected immediately prior to study administration. On-treatment samples was compared to baseline samples with the change from baseline.
Everolimus Trough Concentrations (Cmin)
Cmin values collected prior to dose administration on the same study day and at 20-28 hours after previous dose, at steady state, and patient did not vomit within 4 hours of previous dose. Samples collected during the first 4 days of dosing were excluded from all analyses.
Everolimus Blood Concentrations (C2h) at 2 Hours Post-dose
C2h values collected 1-3 hours after dose administration on the same study day, at steady state, and patient did not vomit between taking previous dose and blood collection. Samples collected during the first 4 days of dosing will be excluded from all analyses.
Time to Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response
Time to angiomyolipoma response was defined as the time from the date of randomization until the date of the first documented angiomyolipoma response. Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; no kidney increases in volume > 20% from nadir; no angiomyolipoma-related bleeding of ≥ grade 2. For the everolimus (core/extension periods) treatment group, the time to angiomyolipoma response is from the start of everolimus. The baseline in the response definition means the latest value on or before starting everolimus.
Duration of Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response
Duration of angiomyolipoma response was defined as the time from the date of the first documented angiomyolipoma response until the date of the first documented angiomyolipoma progression . Angiomyolipoma response was defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume > 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2.
Duration of Skin Lesion Response - Only Everolimus Patients With Best Overall Skin Lesion Response of Complete Clinical Response (CCR) or Partial Response (PR)
Duration of skin lesion response is defined as the time from the date of the first skin lesion response until the date of the first skin lesion progression, according to the PGA (physician's global assessment of clinical condition). A progression is when the disease is worse than at baseline evaluation by >=25% or more.

Full Information

First Posted
November 10, 2008
Last Updated
January 3, 2017
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00790400
Brief 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)
Acronym
EXIST-2
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberous Sclerosis Complex (TSC), Lymphangioleiomyomatosis (LAM)
Keywords
Angiomyolipoma, AML, Tuberous Sclerosis Complex, TSC, mTOR, RAD001, Mammalian Target of Rapamycin, Everolimus, Afinitor, SEGA, Subependymal Giant Cell Astrocytoma, Seizures, Tuberous sclerosis complex (TSC), Tuberous sclerosis, benign tumors of brain, kidney, heart, eyes, lungs, skinTSC1, TSC2, hamaratin, tuberin, tumor growth suppressors, gyri, tubers, Sporadic Lymphangioleiomyomatosis., Lymphangioleiomyomatosis (LAM), rare lung disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
118 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Everolimus
Arm Type
Experimental
Arm Description
Study drug was given by continuous oral daily dosing of two 5 mg tablets.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was given by continuous oral daily dosing of two 5 mg tablets.
Intervention Type
Drug
Intervention Name(s)
Everolimus (RAD001)
Other Intervention Name(s)
RAD001
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Everolimus Placebo
Intervention Description
Matching placebo was provided as a matching tablet and was also blister-packed under aluminum foil in units of ten.
Primary Outcome Measure Information:
Title
Angiomyolipoma Response Rate as Per Central Radiology Review
Description
Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume > 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2. For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.
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 Measure Information:
Title
Time to Angiomyolipoma Progression as Per Central Radiology Review
Description
Time to angiomyolipoma progression (TTAP) is defined as time from date of randomization to date of first documented angiomyolipoma progression. Angiomyolipoma progression was defined as one or more of the following: Increase from nadir of ≥ 25% in angiomyolipoma volume to value greater than baseline; the appearance of a new angiomyolipoma ≥ 1.0 cm in longest diameter; an increase from nadir of 20% or more in the volume of either kidney to a value greater than baseline; angiomyolipoma-related bleeding grade ≥ 2. For the everolimus (core/extension periods) treatment group, the time to angiomyolipoma progression is defined starting from the start of everolimus. The baseline means the latest value on or before starting everolimus.
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
Title
Skin Lesion Response Rate as Per Investigator (Only Patients With at Least One Skin Lesion at Baseline)
Description
Skin lesion response rate in the double-blind period was determined only among patients with at least one skin lesion at baseline, and is the percentage of this group of patients with a best overall skin lesion response on the Physician's Global Assessment of Clinical Condition (PGA) of either complete clinical response (CCR) or partial response (PR). A complete clinical response (CCR) requires a grading of 0 indicating the absence of disease (histological confirmation is not required). Grades 1, 2, and 3 constitute partial response, indicating improvement of at least 50 percent, but less than 100 percent improvement. For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.
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
Title
Percentage of Participants With Renal Impairment
Description
Renal Impairment was measured by glomerular filtration rate which was calculated using the Modification of Diet in Renal Disease formula. Percentage of participants with renal impairment was reported. Severe renal impairment was defined as a GFR of <30ml/min/1.73m2.
Time Frame
Day 1 up to 28 days after end of treatment
Title
Change From Baseline in Plasma Angiogenic Molecules - Vascular Endothelial Growth Factor (VEGF) Marker
Description
Blood samples for biomarker assessment were collected immediately prior to study administration. On-treatment samples was compared to baseline samples with the change from baseline.
Time Frame
4 weeks, 12 weeks, 24 weeks, 36 weeks 48 weeks, 60 weeks, 72 weeks
Title
Everolimus Trough Concentrations (Cmin)
Description
Cmin values collected prior to dose administration on the same study day and at 20-28 hours after previous dose, at steady state, and patient did not vomit within 4 hours of previous dose. Samples collected during the first 4 days of dosing were excluded from all analyses.
Time Frame
Prior to dosing at weeks 2, 4, 12, 24, 48
Title
Everolimus Blood Concentrations (C2h) at 2 Hours Post-dose
Description
C2h values collected 1-3 hours after dose administration on the same study day, at steady state, and patient did not vomit between taking previous dose and blood collection. Samples collected during the first 4 days of dosing will be excluded from all analyses.
Time Frame
2 hours post-dose administration at Weeks 2, 4, 12, 24, 48
Title
Time to Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response
Description
Time to angiomyolipoma response was defined as the time from the date of randomization until the date of the first documented angiomyolipoma response. Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; no kidney increases in volume > 20% from nadir; no angiomyolipoma-related bleeding of ≥ grade 2. For the everolimus (core/extension periods) treatment group, the time to angiomyolipoma response is from the start of everolimus. The baseline in the response definition means the latest value on or before starting everolimus.
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
Title
Duration of Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response
Description
Duration of angiomyolipoma response was defined as the time from the date of the first documented angiomyolipoma response until the date of the first documented angiomyolipoma progression . Angiomyolipoma response was defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume > 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2.
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
Title
Duration of Skin Lesion Response - Only Everolimus Patients With Best Overall Skin Lesion Response of Complete Clinical Response (CCR) or Partial Response (PR)
Description
Duration of skin lesion response is defined as the time from the date of the first skin lesion response until the date of the first skin lesion progression, according to the PGA (physician's global assessment of clinical condition). A progression is when the disease is worse than at baseline evaluation by >=25% or more.
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Barrow Tuberous Sclerosis Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Massachusetts General Hospital Massachussetts General Hospita
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Minnesota Epilepsy Group
City
St. Paul
State/Province
Minnesota
ZIP/Postal Code
55102-2383
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3039
Country
United States
Facility Name
LeBonheur Childrens Medical Group SC-2
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Novartis Investigative Site
City
Torono
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Novartis Investigative Site
City
Lyon
ZIP/Postal Code
69003
Country
France
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10098
Country
Germany
Facility Name
Novartis Investigative Site
City
München
ZIP/Postal Code
80336
Country
Germany
Facility Name
Novartis Investigative Site
City
Siena
State/Province
SI
ZIP/Postal Code
53100
Country
Italy
Facility Name
Novartis Investigative Site
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
ZIP/Postal Code
00137
Country
Italy
Facility Name
Novartis Investigative Site
City
Sapporo-city
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Novartis Investigative Site
City
Suita-city
State/Province
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
Novartis Investigative Site
City
Yamagata
ZIP/Postal Code
990-9585
Country
Japan
Facility Name
Novartis Investigative Site
City
Utrecht
ZIP/Postal Code
3584CX
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
01138
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
04-730
Country
Poland
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
127412
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08025
Country
Spain
Facility Name
Novartis Investigative Site
City
Brighton
State/Province
East Sussex
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Craigavon
State/Province
Northern Ireland
ZIP/Postal Code
BT63 5QQ
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 4XN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SW17 0QT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23312829
Citation
Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Whittemore VH, Chen D, Sahmoud T, Shah G, Lincy J, Lebwohl D, Budde K. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013 Mar 9;381(9869):817-24. doi: 10.1016/S0140-6736(12)61767-X.
Results Reference
background
PubMed Identifier
30192751
Citation
Bissler JJ, Nonomura N, Budde K, Zonnenberg BA, Fischereder M, Voi M, Louveau AL, Herbst F, Bebin EM, Curatolo P, Zonta A, Belousova E. Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. PLoS One. 2018 Sep 7;13(9):e0201005. doi: 10.1371/journal.pone.0201005. eCollection 2018.
Results Reference
derived
PubMed Identifier
30053159
Citation
Bissler JJ, Budde K, Sauter M, Franz DN, Zonnenberg BA, Frost MD, Belousova E, Berkowitz N, Ridolfi A, Christopher Kingswood J. Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2. Nephrol Dial Transplant. 2019 Jun 1;34(6):1000-1008. doi: 10.1093/ndt/gfy132.
Results Reference
derived
PubMed Identifier
29023494
Citation
Sparagana S, Franz DN, Krueger DA, Bissler JJ, Berkowitz N, Burock K, Kingswood JC. Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex. PLoS One. 2017 Oct 12;12(10):e0186235. doi: 10.1371/journal.pone.0186235. eCollection 2017.
Results Reference
derived
PubMed Identifier
26156073
Citation
Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Berkowitz N, Miao S, Segal S, Peyrard S, Budde K. Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial. Nephrol Dial Transplant. 2016 Jan;31(1):111-9. doi: 10.1093/ndt/gfv249. Epub 2015 Jul 8.
Results Reference
derived
Links:
URL
http://www.novartisclinicaltrials.com/webapp/portals/EXISTClinicalTrials/page.do
Description
Visit EXIST-2 NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Learn more about this trial

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

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