Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM

NCT ID: NCT00490789

Last Updated: 2008-04-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-10-31

Study Completion Date

2009-09-30

Brief Summary

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The purpose of this study is to determine the safety and efficacy of the mTOR inhibitor sirolimus as a treatment for renal angiomyolipomas in patients with tyberous sclerosis complex or sporadic lymphangioleiomyomatosis.

Detailed Description

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Inherited mutations of the TSC1 or TSC2 gene cause tuberous sclerosis while acquired (somatic) mutations of either gene are associated with sporadic lymphangioleiomyomatosis (LAM). Renal angiomyolipomas are a feature of both disorders. TSC1 and TSC2 regulate signalling through the mammalian target of rapamycin (mTOR) pathway. Inhibition of mTOR may result in a decrease in size of TSC 1/2 assciated lesions. We are treating patients with tuberous sclerosis or sporadic LAM with the mTOR inhibitor rapamycin in a non-randomised, open label pilot study of safety and efficacy. Change in size of renal angiomyolipomas is the primary end point

Conditions

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Tuberous Sclerosis Lymphangioleiomyomatosis

Keywords

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tuberous sclerosis lymphangioleiomyomatosis sirolimus angiomyolioma rapamycin mTOR

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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sirolimus

daily oral sirolimus with dosage individualised by trough blood levels

Intervention Type DRUG

Other Intervention Names

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rapamune rapamycin

Eligibility Criteria

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Inclusion Criteria

* If female, documentation of negative pregnancy test prior to enrolment.
* Participants, including males, must use an effective form of contraception, whilst taking sirolimus and for twelve weeks after stopping the drug
* One or more renal angiomyolipomata of at least two centimetres or greater in largest diameter
* Adequate renal function :glomerular filtration rate \> 40 ml/min
* Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria) or sporadic LAM (biopsy-proven or compatible high resolution chest CT scan and respiratory function tests.)
* Signed and dated informed consent

Exclusion Criteria

* History of non-compliance or inability to give informed consent
* Significant haematological or hepatic abnormality (i.e. transaminase levels \> 150 i.u./L serum albumin \< 30 g/L, haematocrit\< 30%, platelets \< 100,000/ mm3, adjusted absolute neutrophil count \< 1,500/mm3, total WBC \< 3,000/ mm3)
* Greater than 1 g proteinuria daily
* Multiple bilateral AMLs, where individual lesions cannot be distinguished
* Renal haemorrhage within preceding year
* In those who have had a renal haemorrhage, known conservatively managed renal aneurysm(s) greater than 10mm
* Patients who have had embolisation for AML(s) within the preceding 6 months
* Patients who are unable to walk 100 metres on the flat
* Continuous requirement for supplemental oxygen
* Patients who have had or are being considered for organ transplant
* Uncontrolled hyperlipidaemia
* Intercurrent infection at initiation of Sirolimus
* Surgery within last 2 months
* Pregnant or lactating women
* Use of an investigational drug within the last 30 days
* Change in anti epileptic drug medication within the last 3 months
* Likely to need vaccination e.g. for travel during the course of the trial (except for influenza vaccine in patients with LAM)
* Current usage of strong inhibitors of CYP3AE ( such as ketoconazole, voriconazole, itraconazole, tilithromycin or clarithromycin) or strong inducers (such as rifampicin or rifabutin)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Nottingham

OTHER

Sponsor Role collaborator

St Georges Hospital Medical School

UNKNOWN

Sponsor Role collaborator

Royal Sussex County Hospital

OTHER

Sponsor Role collaborator

The Tuberous Sclerosis Association

OTHER

Sponsor Role collaborator

Wyeth is now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role collaborator

Cardiff University

OTHER

Sponsor Role lead

Responsible Party

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Cardiff University

Principal Investigators

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Julian R Sampson, DM

Role: PRINCIPAL_INVESTIGATOR

Cardiff Univeristy

Locations

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University Hospital of Wales

Cardiff, Wales, United Kingdom

Site Status

Royal Sussex County Hospital

Brighton, , United Kingdom

Site Status

City Hospital

Nottingham, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Davies DM, de Vries PJ, Johnson SR, McCartney DL, Cox JA, Serra AL, Watson PC, Howe CJ, Doyle T, Pointon K, Cross JJ, Tattersfield AE, Kingswood JC, Sampson JR. Sirolimus therapy for angiomyolipoma in tuberous sclerosis and sporadic lymphangioleiomyomatosis: a phase 2 trial. Clin Cancer Res. 2011 Jun 15;17(12):4071-81. doi: 10.1158/1078-0432.CCR-11-0445. Epub 2011 Apr 27.

Reference Type DERIVED
PMID: 21525172 (View on PubMed)

Other Identifiers

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TESSTAL

Identifier Type: -

Identifier Source: org_study_id