Condition category
Cancer
Date applied
04/02/2008
Date assigned
04/02/2008
Last edited
29/10/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://rarediseasesnetwork.epi.usf.edu/rldc/centers/uhn-toronto.htm

Contact information

Type

Scientific

Primary contact

Dr Gregory Paul Downey

ORCID ID

Contact details

11C-1183
Toronto General Hospital
Toronto
Ontario
M5G 1L7
Canada
+1 416 340 4996
gregory.downey@uhn.on.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00414648

Protocol/serial number

MCT-83051

Study information

Scientific title

Sirolimus Multicentre International Lymphangioleiomyomatosis Efficacy and Safety: Canadian component - a placebo-controlled, randomised, parallel group trial

Acronym

MILES

Study hypothesis

1. Implement a double-blind, placebo-controlled, 'intention to treat' based, multicentre protocol for the determination of the safety and efficacy of sirolimus in patients with lymphangioleiomyomatosis (LAM)
2. Determine the correlation between changes in lung function and questionnaire-based assessments of dyspnoea, quality of life, fatigue, and degree of health impairment in LAM trial patients who are taking sirolimus or placebo

Ethics approval

1. Research Ethics Board of University Health Network, Toronto (Canada) approved on 07/12/2007 (ref: 07-095-A)
2. Institutional Review Board of Niigata University Medical and Dental Hospital (Japan) approved on the 24/07/2007 (ref: NH19-003)
3. Institutional Review Board (Federalwide Assurance # 00002988) of Cincinnati Children’s Hospital Medical Center, Cincinnati (USA) approved on 11/01/2008 (ref: 04-11-17)

Ethics approval from Australia pending.

Study design

International, multicentre, placebo-controlled, randomised, parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Lymphangioleiomyomatosis (LAM)

Intervention

This is a multicentre, international, intention to treat, placebo-controlled, randomised parallel, drug/diagnostic, efficacy and safety trial with study participant, study investigator, caregiver, outcome assessor, and data analyst blinded.

1. Experimental group: sirolimus (rapamycin), daily dose of 2 mg during 12 months; follow up only for additional 12 months
2. Control group: matching placebo of active treatment, 1 pill daily for 12 months; follow up only for additional 12 months

Contact for public queries same as below. Please note that you can also contact Dr
Lianne Singer at lianne.singer@uhn.on.ca for details on this trial (scientific and public queries).

Intervention type

Drug

Phase

Not Applicable

Drug names

Sirolimus (rapamycin)

Primary outcome measures

FEV1 slope response, measured at 12 months.

Secondary outcome measures

Measured at 12 months:
1. Six minute walk testing
2. Quantitative CT of the lung
3. Quality of life questionnaires (St George Respiratory Questionnaire, 36-item short form health survey [SF-36])
4. Forced vital capacity (FVC)
5. Diffusing capacity of the lung for carbon monoxide (DLCO)

Overall trial start date

01/06/2007

Overall trial end date

31/12/2010

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women, aged 18 years and older
2. Signed and dated informed consent
3. Diagnosis of LAM as determined by biopsy (lung, abdominal mass, lymph node or kidney) and chest computed tomography [CT] scan findings compatible with LAM; or compatible chest CT scan findings in the setting of tuberous sclerosis, angiomyolipomata (diagnosed by CT, magnetic resonance imaging [MRI] or biopsy), or chylous pleural effusion (verified by thoracentesis)
4. Forced expiratory volume in one second (FEV1) less than or equal to 70% of predicted during baseline visit after bronchodilator

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

260

Participant exclusion criteria

1. History of myocardial infarction, angina or stroke related to atherosclerosis
2. Pregnancy or breast feeding, inadequate contraception
3. Significant haematologic or hepatic abnormality (i.e., transaminase levels greater than 3 times the upper limit of normal range, haematocrit [HCT] less than 30%, platelets less than 80,000/cumm, adjusted absolute neutrophil count less than 1,000/cumm, total white blood cell count [WBC] less than 3,000/cumm)
4. Intercurrent infection at initiation of sirolimus
5. Recent surgery 2 months (involving entry into a body cavity or requiring sutures)
6. Use of an investigational drug within the last 30 days
7. Uncontrolled hyperlipidaemia
8. Previous lung transplantation
9. Inability to attend scheduled clinic visits
10. Inability to give informed consent
11. Inability to perform pulmonary function testing
12. Creatinine greater than 2.5 mg/dl (greater than 220 µmol/L)
13. Chylous ascites sufficient to affect diaphragmatic function on pulmonary function tests (PFTs)
14. Pleural effusion sufficient to affect pulmonary function based on the opinion of the Site Investigator (generally greater than 500 cc)
15. Acute pneumothorax within the past 2 months (as pneumothorax can alter baseline PFT results)
16. History of malignancy in the past two years, other than squamous or basal cell skin cancer
17. Use of oestrogen containing medications

Recruitment start date

01/06/2007

Recruitment end date

31/12/2010

Locations

Countries of recruitment

Australia, Canada, Japan, United States of America

Trial participating centre

11C-1183
Toronto, Ontario
M5G 1L7
Canada

Sponsor information

Organisation

University Health Network (Toronto) (Canada)

Sponsor details

200 Elizabeth Street
Toronto
Ontario
M5G 2C4
Canada

Sponsor type

Research organisation

Website

http://www.uhn.ca/index.htm

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-83051)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21410393
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24159565

Publication citations

  1. Results

    McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC, , , Efficacy and safety of sirolimus in lymphangioleiomyomatosis., N. Engl. J. Med., 2011, 364, 17, 1595-1606, doi: 10.1056/NEJMoa1100391.

  2. Results

    Young L, Lee HS, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP, Goldberg HJ, Downey GP, Swigris JJ, Taveira-DaSilva AM, Krischer JP, Trapnell BC, McCormack FX, , Serum VEGF-D a concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial., Lancet Respir Med, 2013, 1, 6, 445-452, doi: 10.1016/S2213-2600(13)70090-0.

Additional files

Editorial Notes