UMIN-CTR Clinical Trial

Public title

A multicenter, phase 3 study assessing efficacy and safety of the Sirolimus in the Treatment of intractable lymphatic anomalies (SILA study)

Acronym

Sirolimus for Intractable Lymphatic Anomalies

Scientific Title

A multicenter, phase 3 study assessing efficacy and safety of the Sirolimus in the Treatment of intractable lymphatic anomalies (SILA study)

Scientific Title:Acronym

Sirolimus for Intractable Lymphatic Anomalies

Region

Japan

Condition

Intractable Lymphatic Anomalies

Classification by specialty

Hematology and clinical oncology	Vascular surgery	Pediatrics

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To assess efficacy and safety of mTOR inhibitor sirolimus in patients with intractable lymphatic anomalies.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase III

Primary outcomes

Target lesion response rate determined by Independent Review Facility after 52 weeks of treatments

Key secondary outcomes

Target lesion response rate determined by Independent Review Facility after 12, 24 weeks of treatments
Respiratory function after 12, 24 and 52 weeks of treatments
Evaluation of pleural effusion after 12, 24 and 52 weeks of treatments
Evaluation of ascites after 12, 24 and 52 weeks of treatments
Blood coagulation parameters after 12, 24 and 52 weeks of treatments
Bleeding after 12, 24 and 52 weeks of treatments
Pain after 12, 24 and 52 weeks of treatments
QOL improvement rates after 12, 24 and 52 weeks of treatments
ADL improvement rates after 12, 24 and 52 weeks of treatments
Adverse events and side effects
Laboratory values
Vital signs
Pharmacokinetics

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

NO

Dynamic allocation

NO

Institution consideration

Blocking

NO

Concealment

No need to know

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Body surface area (BSA) >= 1.0m2: an initial dose of sirolimus (2mg/day) is single orally administered under fed or fasting condition. Subsequently, the sirolimus dosage is adjusted to achieve trough levels between 5-15 ng/mL. Maximum dose of sirolimus is 4 mg per day.
BSA < 1.0m2: an initial dose of sirolimus (1mg/day) is single orally administered under fed or fasting condition. Subsequently, the sirolimus dosage is adjusted to achieve trough levels between 5-15 ng/mL. Maximum dose of sirolimus is 4 mg per day.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients with BSA >= 0.6m2 at entry and judged by the investigator/subinvestigator to be able to take tablets
2) Patients definitively diagnosed with lymphangioma (cystic lymphatic malformation) who have craniocervical, intraperitoneal or retroperitoneal cystic lesions, lymphangiomatosis (generalized lymphatic anomaly) or Gorham-Stout disease according to the diagnostic criteria
3) Patients having one or more measurable lesions evaluated by pretreatment MR imaging
4) Patients must have lymphatic anomalies that have potential to cause significant morbidity.
5) Normal liver, renal, and cardiac function at entry
Total bilirubin < 3 x ULN for age
CRE < 3 x ULN for age
6) Written consent to participate in this clinical trial has been given by the subject in person or by a legal guardian (when the subject is younger than 20 years at consent).

Key exclusion criteria

1) Past usage of mTOR inhibitors or other molecular target drugs relating mTOR pathway within 8 weeks
2) Patients who currently have an uncontrolled infection
3) Karnofsky Performance Status (PS) <= 30 (10 years of age) or Lansky play PS <= 30 (< 10 years of age)
4) Uncontrolled diabetes, uncontrolled hypertension, uncontrolled hyperlipidemia, chronic liver disease, or chronic renal disease
5) Chronic treatment (>= 4 weeks) with systemic steroids or another immunosuppressive agent at entry. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary.
6) History of allergy to sirolimus, or additive substance
7) Patients must also avoid strong inducers of CYP3A4, and may not have received these medications within 1 week of entry.
8) Known history of HIV seropositivity or known immunodeficiency
9) Hepatitis B virus carrier and/or Hepatitis C virus carrier
10) Malabsorption of sirolimus
11) Patients who have undergone surgical resection or interventional radiology procedures for target lesions within 2 weeks
12) Patients who have received therapeutic medication for a target disease within 2 weeks
13) Patients who have received chemotherapy drugs that cause bone marrow suppression, biological drug, or off-label products within 4 weeks
14) Patients who have received radiation therapy for target lesions within 24 weeks
15) Patients who have participated another clinical trial within 4 weeks
16) Patients who have dental braces or prosthesis only if it interferes with radiologic analysis of lymphatic anomaly
17) Pregnant, probably pregnant, or breast-feeding woman.
Patients who do not agree birth control during clinical trial.
18) Patient who is judged inappropriate to participate in this study by the investigators

Target sample size

10

Name of lead principal investigator

1st name
Middle name
Last name	Michio Ozeki

Organization

Gifu University Hospital

Division name

Pediatrics

Zip code

Address

1-1 Yanagido, Gifu City 501-1194, Japan

TEL

058-230-6000

Email

michioo@gifu-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Ryuta Asada

Organization

Gifu University Hospital

Division name

Innovative and Clinical Research Promotion Center

Zip code

Address

1-1 Yanagido, Gifu City 501-1194, Japan

TEL

058-230-6000

Homepage URL

Email

rasada@gifu-u.ac.jp

Institute

Gifu University

Institute

Department

Personal name

Organization

AMED

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

慶應義塾大学病院（東京都）
国立成育医療研究センター（東京都）
岐阜大学医学部附属病院（岐阜県）
京都府立医科大学附属病院（京都府）
九州大学病院（福岡県）

Date of disclosure of the study information

2017

Year

08

Month

30

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

06

Month

15

Day

Date of IRB

2017

Year

07

Month

11

Day

Anticipated trial start date

2017

Year

10

Month

01

Day

Last follow-up date

2019

Year

08

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

08

Month

30

Day

Last modified on

2021

Year

03

Month

02

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033078