Safety and Efficacy of Everolimus (Afinitor®) in Chinese Adult Patients With Angiomyolipoma Associated With Tuberous Sclerosis Complex.

Phase 4

Completed

Conditions: Renal Angiomyolipoma

Interventions: Drug: Everolimus

Registration Number: NCT03525834

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of this study was to assess the safety and efficacy of everolimus (Afinitor®) in Chinese patients with renal angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC).

Detailed Description: This was an open label, single arm, multi-center, Phase IV Post-Approval Commitment (PAC) study with once daily oral dose of 10 mg everolimus in participants with renal AML associated with TSC. There were three separate phases in this study: a Screening phase, an Open-label treatment phase where participants received everolimus for 48 weeks or until disease progression, and a Treatment discontinuation follow-up phase for patients who discontinue study drug for reasons other than disease progression. Every participant had an End of Treatment visit within 28 days after last dose and a safety follow-up visit 30 days after last dose.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

Inclusion Criteria

Eligible for treatment with everolimus as per the locally approved label.
Presence of at least one AML ≥ 3 cm in its longest diameter using CT or MRI.

Exclusion Criteria

AML related bleeding or embolization during the 6 months prior to enrollment.
History of myocardial infarction, angina or stroke related to atherosclerosis.
Impaired lung function.
Significant hematological or hepatic abnormality.
Any severe and/or uncontrolled medical conditions.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Everolimus	Everolimus	Participants targeted to receive Everolimus tablets 10 mg orally once daily for 48 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 52 weeks	Percentage of participants with AEs and SAEs including significant changes from baseline in vital signs, electrocardiograms and laboratory parameters (laboratory assessments included hematology, biochemistry, coagulation and urinalysis) qualifying and reported as AEs. The percentage of participants in each category is reported in the table.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With NCI CTCA Grade 3/4 Serum Creatinine	Baseline, 48 weeks	NCI CTCAE grade 3/4 serum creatinine is defined as \> 3.0 x upper limits of normal (ULN). Serum creatinine was measured at baseline and at four other time points; only the worst post-baseline value for every participant was counted (highest value for serum creatinine).
Percentage of Participants With Best Overall Response (BOR) Status of Angiomyolipoma (AML) Response During Maximum Treatment Duration of 48 Weeks	Baseline, 48 weeks	BOR status is the best status recorded from start of treatment until disease progression. AML response status: reduction in AML volume of at least 50% relative to screening AML. 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 4.03). Up to five of the largest measurable lesions (≥ 1 cm in longest diameter) in each kidney were measured at screening via Magnetic Resonance Imaging/Computed tomography (MRI/CT) and were defined as screening AML. The sum of the volumes of these individual lesions was defined as AML volume and it was measured at each assessment during the trial. Increases in the AML volume were evidence of worsening AML, decreases were evidence of clinical response.
Percentage of Participants With Best Overall Response Status of Angiomyolipoma (AML) Progression During Maximum Treatment Duration of 48 Weeks	Baseline, 48 weeks	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 4.03). Up to five of the largest measurable lesions (≥ 1 cm in longest diameter) in each kidney were measured at screening via Magnetic Resonance Imaging/Computed tomography (MRI/CT) and were defined as screening AML. The sum of the volumes of these individual lesions was defined as AML volume and it was measured at each assessment during the trial. Increases in the AML volume were evidence of worsening AML.
Percentage of Participants With Severe Renal Impairment	Baseline, 48 weeks	Renal impairment is defined as calculated Creatinine Clearance (CrCl) \< 30 mL/min. CrCl was measured at baseline and at four other time points; only the baseline and the worst post-baseline value for every participant were counted (lowest value for CrCl). Creatinine clearance was estimated using the Cockcroft-Gault formula: creatinine clearance (mL/minute) = urine creatinine concentration (mL/dL) x volume of urine (mL/24 hour) / plasma creatinine concentration (mg/dL) x 1440 minute/24 hour