Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Sclerosis

Tuberous Sclerosis

Angiomyolipoma

Hamartoma

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Neoplasms, Adipose Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Perivascular Epithelioid Cell Neoplasms

Tuberous Sclerosis Complex

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Anti-Infective Agents

Everolimus

Liver Extracts

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Participants with confirmed diagnosis of TSC-AML and who fulfil the local (Taiwan) reimbursement criteria of everolimus for TSC-AML treatment

Everolimus tablets for oral use. The recommended everolimus starting dose will be 10 mg orally taken once daily for all patients, except for those with impaired liver function, for whom the everolimus dose will be:

* Child-Pugh grade A: 7.5 mg once daily (for patients with mild hepatic impairment)
* Child-Pugh grade B: 5.0 mg once daily (for patients with moderate hepatic impairment)

Novartis Pharmaceuticals

The purpose of this prospective study is to assess the safety and efficacy of everolimus in Taiwanese patients with renal angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC) . Only patients who fulfil the local reimbursement criteria of everolimus for TSC-AML will be included in this study.

This open-label, prospective, single-arm, multicenter Phase IV post approval commitment (PAC) study is planned to be conducted in approximately 10 patients with confirmed diagnosis of TSC-AML and who fulfil the local reimbursement criteria of everolimus for TSC-AML treatment.

The study will have a 30-day screening phase, and each patient will be on treatment up to 52 weeks. Enrollment will end at the latest within 52 weeks from Day 1 of the study, regardless of the number of patients actually recruited. After completion of the treatment phase/end of treatment (EOT), eligible patients will enter a 4-week safety follow up (FU) phase. Patients who continue to be on treatment beyond 52 weeks, based on the investigator's judgment will not be included in the 4-week safety FU phase.

A Phase IV Study of Safety and Efficacy of Everolimus in Taiwanese Patients With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma (TSC-AML)

Phase IV, Prospective Single Arm Study of Safety and Efficacy of Votubia (Everolimus) in Taiwanese Adults With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Percentage of participants with AEs, SAEs and AESIs.

AML response rate is defined as the percentage of patients with an AML response. AML response will be defined as: A reduction in AML volume of at least 50% relative to screening, where AML volume is the sum of the volumes of all target AML identified at screening. In addition, AML response have to satisfy: no new AML ≥ 1 cm in longest diameter are identified, neither kidney increases in volume by more than 20% from nadir (where nadir is the lowest kidney volume at the screening), the participant does not have any angiomyolipoma-related bleeding of grade equal or over 2 (as defined by NCI CTCAE, version 5).

AML progression rate is defined as the percentage of patients with an AML progression. AML progression status is defined as one or more of the following: an increase from nadir of 25% or more in AML volume to a value greater than screening AML (where nadir is the lowest AML volume obtained for the participant previously in the trial), the appearance of a new AML ≥ 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 screening (where nadir is the lowest kidney volume obtained for the participant previously in the trial), angiomyolipoma-related bleeding grade ≥2 (as defined by NCI CTCAE, version 5)

The laboratory assessment (including hematology, coagulation, biochemistry, and urinalysis) will be recorded at baseline and during the study based on changes in grade of laboratory abnormality.

Blood and Lymph Conditions

Immune System Diseases

Facies

Lymphangioleiomyomatosis

Fibroma

Astrocytoma

Angiofibroma

Rhabdomyoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Lymphangiomyoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Vascular Tissue

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Myoma

Subependymal Giant Cell Astrocytoma

Neuroepithelioma

Üarticipants diagnosed with Tuberous Sclerosis Complex (TSC) aged between 2 months and 50 years.

Peter Bauer, Prof.Dr

International, multicenter, observational, longitudinal study to identify biomarker/s for Tuberous Sclerosis Complex and to explore the clinical robustness, specificity, and long´-term variability of these biomarker/s

Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder characterized by the growth of numerous tumors in different body parts related to dysregulation of the mechanistic target of rapamycin (mTOR) pathway. The overall incidence of TSC is estimated to be as high as 1 in 6000 to 10,000 live birth.The main aspects of TSC that influence the quality of life are associated with the brain: seizures, evelopmental delay, intellectual disability, and autism. However, the incidence and severity of the various aspects of TSC can vary widely.

TSC is generally caused by pathogenic variants in the tumor suppressor genes: TSC1 and TSC2. Confirmation of a clinical diagnosis of tuberous sclerosis is performed via TSC1 and TSC2 sequencing.

There is no cure for TSC, therefore symptomatic therapy is the best possible choice, including mTOR inhibitors, vigabatrin and other antiepileptic drugs for the seizures, and neurosurgery in cases of life-threatening neurological symptoms.

The aim of the study is established TSC specific biomarker/s. Such biomarkers aim to facilitate the diagnosis, treatment personalization and monitoring.

Blood sample applied on the Dry Blood Spot (DBS) Filtercard (Centocard®)

Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)

Biomarkers for Tuberous Sclerosis Complex: An International Multicenter Observational Longitudinal Protocol

All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.

Samples will be analyzed for the candidate biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC.

CENTOGENE GmbH Rostock

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase IV Study of Safety and Efficacy of Everolimus in Taiwanese Patients With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma (TSC-AML)	NCT05252585	Renal Angiomyol...	Everolimus	20 Years - 65 Years	Novartis
Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)	NCT02654340	Hypomelanotic M... Facial Angiofib... Shagreen Patche... Ungual Fibromas Cortical Dyspla... Cardiac Rhabdom... Lymphangioleiom... Renal Angiomyol... Subependymal Gi...		2 Years - 50 Years	CENTOGENE GmbH Rostock
A Phase IV Study of Safety and Efficacy of Everolimus in Taiwanese Patients With Tuberous Sclerosis Complex Who Have Renal Angiomyolipoma (TSC-AML)	NCT05252585	Renal Angiomyol...	Everolimus	20 Years - 65 Years	Novartis
Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)	NCT02654340	Hypomelanotic M... Facial Angiofib... Shagreen Patche... Ungual Fibromas Cortical Dyspla... Cardiac Rhabdom... Lymphangioleiom... Renal Angiomyol... Subependymal Gi...		2 Years - 50 Years	CENTOGENE GmbH Rostock
Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)	NCT02654340	Hypomelanotic M... Facial Angiofib... Shagreen Patche... Ungual Fibromas Cortical Dyspla... Cardiac Rhabdom... Lymphangioleiom... Renal Angiomyol... Subependymal Gi...		2 Years - 50 Years	CENTOGENE GmbH Rostock

Spots Global Cancer Trial Database for renal angiomyolipoma