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

NCT00490789

Last updated date
Study Location
University Hospital of Wales
Cardiff, Wales, CF14 4XN, United Kingdom
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Tuberous Sclerosis, Lymphangioleiomyomatosis
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-65 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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)

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Tuberous Sclerosis, LymphangioleiomyomatosisTrial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM
NCT00490789
  1. Cardiff, Wales
  2. Brighton,
  3. Nottingham,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM
Official Title  ICMJE A Trial of the Efficacy and Safety of Sirolimus(Rapamycin)Therapy for Renal Angiomyolipmoas in Patients With Tuberous Sclerosis Complex and Sporadic Lymphangioleiomyomatosis
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.
Detailed Description 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Tuberous Sclerosis
  • Lymphangioleiomyomatosis
Intervention  ICMJE Drug: sirolimus
daily oral sirolimus with dosage individualised by trough blood levels
Other Names:
  • rapamune
  • rapamycin
Study Arms  ICMJE Not Provided
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 21, 2007)
14
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2009
Estimated Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00490789
Other Study ID Numbers  ICMJE TESSTAL
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Julian R Sampson, Cardiff University
Study Sponsor  ICMJE Cardiff University
Collaborators  ICMJE
  • University of Nottingham
  • St Georges Hospital Medical School
  • Royal Sussex County Hospital
  • The Tuberous Sclerosis Association
  • Wyeth is now a wholly owned subsidiary of Pfizer
Investigators  ICMJE
Principal Investigator:Julian R Sampson, DMCardiff Univeristy
PRS Account Cardiff University
Verification Date April 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP