Neoplasms

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Astrocytoma

Sclerosis

Tuberous Sclerosis

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

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

Tuberous Sclerosis Complex

Subependymal Giant Cell Astrocytoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

As this was a non-randomized, open-label, single arm study, all patients in the study received treatment with everolilmus

Initial everolimus dosage will be 3 mg/m2/d taken daily or every other day, with titration to achieve a trough serum level of 5-15 ng/ml. Patients unable to tolerate levels in this range will have doses held or reduced 25% to achieve trough serum levels of 5-10 ng/ml. If trough serum level of 5-15 ng/ml is not achieved at a dosage of 3 mg/m2/d, then dosage escalation by 25% will be undertaken as tolerated. Everolimus will be similarly adjusted during the extension phase. If a subject misses more than 10 consecutive everolimus doses, additional days of everolimus treatment will be added so total duration of treatment is 6 months. If this occurs, dates of subsequent study events will be adjusted according to number of missed doses. This process will also be followed in the extension phase.

David N Franz, M.D.

The purpose of the study is to evaluate the safety and potential side effects of everolimus (an experimental drug) on a person with Tuberous Sclerosis Complex who also has been diagnosed with a brain tumor (astrocytoma)

The hypothesis is that the drug will cause the tumor size to decrease, and may have beneficial activity separate from effects on tumors in patients.

Tuberous Sclerosis Complex (TSC)is a genetic disorder with a birth incidence of approximately one in six thousand. Five to twenty percent of patients with TSC will develop astrocytoma, a slowly progressive tumor. They grow and cause damage to surrounding brain tissue, blockage of spinal fluid (hydrocephalus), blindness, trouble walking, seizures, and brain damage. If untreated, they can be fatal. Standard treatment involves surgery to remove the tumor; however surgery may itself cause brain damage, bleeding, or infection, as well as other complications. Studies have shown that everolimus suppresses the chemicals that cause tumors to grow in tuberous sclerosis, and may cause them to shrink.

The primary objective of this study is to find out the effects of everolimus on astrocytomas in a six month trial in patients with Tuberous Sclerosis who have been diagnosed with an astrocytoma

Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex

Everolimus (RAD001)Therapy of Giant Cell Astrocytomas in Patients With Tuberous Sclerosis Complex

Novartis

Children's Hospital Medical Center, Cincinnati

This was a non-randomized, open-label, single arm study; all patients in the study received treatment with everolimus.

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. David Franz

Upper Respiratory Tract Infection

Stomatitis

Sinusitis

Mouth Ulceration

Cellulitis

Diarrhoea

Gastroenteritis

Otitis Media

Pyrexia

Vomiting

Acne

Convulsion

Nasopharyngitis

Rhinitis Allergic

Conjunctivitis

Pharyngitis

Rash

Constipation

Cough

Dermatitis Acneiform

Dermatitis Contact

Excoriation

Laceration

Nasal Congestion

Otitis Externa

Abnormal Behaviour

Body Tinea

Dry Skin

Pneumonia

Skin Infection

Urinary Tract Infection

This was a non-randomized, open-label, single arm study; all patients in the study received treatment with everolimus. The initial starting dose was to be 3.0 mg/m2/day taken either daily or every other day with titration to achieve target trough concentrations of 5 to 15 ng/mL, subject to tolerability. Study drug was self-administered orally (or administered by a caregiver) at the same time each day.

Number With Observed Adverse Side Effects

# with reductions > 30% relative to baseline

# with reductions > 50% relative to baseline

Overall Reduction in SEGA Tumor Volume.

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

WXFL10030390 continuous oral dosing (0.1 mg once a day)

WXFL10030390 continuous oral dosing (0.2 mg once a day)

WXFL10030390 continuous oral dosing (0.4 mg once a day)

WXFL10030390 continuous oral dosing (0.7 mg once a day)

WXFL10030390 continuous oral dosing (1.1 mg once a day)

WXFL10030390 continuous oral dosing (1.4 mg once a day)

WXFL10030390 continuous oral dosing (1.7 mg once a day)

WXFL10030390 is a tablet in the form of 0.1mg and 0.5mg, oral, once a day.

WXFL10030390

Jin Li, Doctor

WXFL10030390 (WX390) is a novel oral small molecular that inhibits phosphoinositide-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) and has demonstrated potent inhibitory effects on multiple human tumor xenografts. The first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of WX390 at single dose and multiple doses.

This study will be an open-lable, phase Ⅰ study and will evaluate the safety and pharmacokinetics of WX390 after a single administration followed by a 28-day continuous course of therapy; evaluate the safety and preliminary efficacy in an open-lable administration of WX390 at the MTD.

A Study of WXFL10030390 in Patients With Advanced Solid Tumors or Lymphoma

A Phase Ⅰ Study of PI3K/mTOR Dual Inhibitor WXFL10030390 to Evaluate the Safety, Tolerability and Pharmacokinetics in Patients With Advanced Solid Tumors or Lymphoma

The safety and tolerability of WXFL10030390 will be evaluated based on adverse events data. Other safety parameters include physical examination, clinical laboratory tests including coagulation function, renal function, hepatic function, blood glucose and blood lipid.

Cmax will be determined for an oral administration of WXFL10030390 tablets.

tmax will be determined for an oral administration of WXFL10030390 tablets.

AUC will be determined for an oral administration of WXFL10030390 tablets.

t½ will be determined for an oral administration of WXFL10030390 tablets.

The recommended phase 2 dose (RP2D) of WXFL10030390 will be determined based on pharmacokinetics, safety and tolerability, as well as preliminary efficacy.

The sum of complete responses (CR) + partial responses (PR) + stable disease (SD) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) or Lugano 2014 criteria

Defined as complete response \[CR\] + partial response \[PR\]) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) or Lugano 2014 criteria

Shanghai Jiatan Pharmatech Co., Ltd

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex	NCT00411619	Tuberous Sclero... Subependymal Gi...	Everolimus	3 Years -	Children's Hospital Medical Center, Cincinnati
A Study of WXFL10030390 in Patients With Advanced Solid Tumors or Lymphoma	NCT03730142	Advanced Cancer	WXFL10030390	18 Years - 75 Years	Shanghai Jiatan Pharmatech Co., Ltd
Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex	NCT00411619	Tuberous Sclero... Subependymal Gi...	Everolimus	3 Years -	Children's Hospital Medical Center, Cincinnati
A Study of WXFL10030390 in Patients With Advanced Solid Tumors or Lymphoma	NCT03730142	Advanced Cancer	WXFL10030390	18 Years - 75 Years	Shanghai Jiatan Pharmatech Co., Ltd

Spots Global Cancer Trial Database for mammalian target of rapamycin (mtor)