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

• Status: Unknown status
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cardiff University
• Collaborators: Royal Sussex County Hospital; St Georges Hospital Medical School; The Tuberous Sclerosis Association; University of Nottingham; Wyeth is now a wholly owned subsidiary of Pfizer
• Treatments: Everolimus; Sirolimus

Criteria

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)