NCT00490789

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
14

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Oct 2005

Typical duration for phase_2

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2005

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

June 21, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 25, 2007

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2009

Completed
Last Updated

April 30, 2008

Status Verified

April 1, 2008

Enrollment Period

3.9 years

First QC Date

June 21, 2007

Last Update Submit

April 29, 2008

Conditions

Keywords

tuberous sclerosislymphangioleiomyomatosissirolimusangiomyoliomarapamycinmTOR

Outcome Measures

Primary Outcomes (2)

  • longest diameter of renal angiomyolipomas assessed by MRI scan, toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0

    assessments at baseline and 2,6,12 and 24 months

  • toxicity graded by National Cancer Institute's Common Terminology Criteria for Adverse Events

    throughout study

Secondary Outcomes (1)

  • respiratory function tests (FEV1, FVC, DLCO), cognitive function (memory, executive skills)

    2 years

Interventions

daily oral sirolimus with dosage individualised by trough blood levels

Also known as: rapamune, rapamycin

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University Hospital of Wales

Cardiff, Wales, CF14 4XN, United Kingdom

Location

Royal Sussex County Hospital

Brighton, BN2 5BE, United Kingdom

Location

City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Tuberous SclerosisLymphangioleiomyomatosis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

HamartomaNeoplasmsNeoplasms, Multiple PrimaryNeoplastic Syndromes, HereditaryMalformations of Cortical Development, Group IMalformations of Cortical DevelopmentNervous System MalformationsNervous System DiseasesNeurocutaneous SyndromesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, InbornLymphangiomyomaNeoplasm, Lymphatic TissueNeoplasms by Histologic TypePerivascular Epithelioid Cell NeoplasmsNeoplasms, Connective and Soft TissueLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic Chemicals

Study Officials

  • Julian R Sampson, DM

    Cardiff Univeristy

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

June 21, 2007

First Posted

June 25, 2007

Study Start

October 1, 2005

Primary Completion

September 1, 2009

Study Completion

September 1, 2009

Last Updated

April 30, 2008

Record last verified: 2008-04

Locations