UMIN-CTR Clinical Trial

Unique ID issued by UMIN	UMIN000025901
Receipt number	R000029596
Scientific Title	Placebo-controlled randomized, double-blind study of zaltoprofen for patients with diffuse type tenosynovial giant cell tumor (Pigmented Villonodular Synovitis) and unresectable localized tenosynovial giant cell tumor (tendon sheath giant cell tumor) (Phase II study)
Date of disclosure of the study information	2017/04/01
Last modified on	2023/01/12 10:30:05

* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments

Basic information

Public title

Placebo-controlled randomized, double-blind study of zaltoprofen for patients with diffuse type tenosynovial giant cell tumor (Pigmented Villonodular Synovitis) and unresectable localized tenosynovial giant cell tumor (tendon sheath giant cell tumor) (Phase II study)

Acronym

Placebo-controlled randomized, double-blind Phase II study of zaltoprofen for patients with diffuse type tenosynovial giant cell tumor and unresectable localized tenosynovial giant cell tumor

Scientific Title

Scientific Title:Acronym

Placebo-controlled randomized, double-blind Phase II study of zaltoprofen for patients with diffuse type tenosynovial giant cell tumor and unresectable localized tenosynovial giant cell tumor

Region

Japan

Condition

diffuse type tenosynovial giant cell tumor (Pigmented Villonodular Synovitis) and localized tenosynovial giant cell tumor (tendon sheath giant cell tumor)

Classification by specialty

Orthopedics

Classification by malignancy

Others

Genomic information

Objectives

Narrative objectives1

Evaluation of efficacy and safety of zaltoprofen for for patients with diffuse type tenosynovial giant cell tumor (Pigmented Villonodular Synovitis) and unresectable localized tenosynovial giant cell tumor (tendon sheath giant cell tumor)

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase II

Assessment

Primary outcomes

Progression-free rate at 48 weeks after drug administration ((Definition of exacerbation is "serious event requiring surgical intervention")
Evaluate as exacerbation if it falls under any one or more of the following serious events requiring surgical intervention. If (1) and (2) are evaluated every 4 weeks and judged as exacerbation twice in succession, if (3), (4), (5) are evaluated once every 12 weeks and evaluated once Judgment of exacerbation.
1) Increase in joint perimeter diameter by 2 cm or more with respect to baseline (knee is 1 cm above knee patella, ankle joint is measuring using figure-eight method). If there is fluid accumulation, puncture to check for the presence or absence of hematoma, increase in joint periphery diameter due to edema is not exacerbated.
(2) The range of motion of the joint (active motion) is reduced by 20% or more with respect to the baseline (calculated by averaging three measurements with a goniometer)
(3) Invasion of 5 mm or more of bone / cartilage erosion or new lesion of bone / cartilage erosion of 5 mm or more compared with baseline by CT or MRI
(4) X-ray photography at standing position, disappearance of joint space
(5) Increase of target lesion by 20% or more by RECIST
(6) Other cases, surgery was performed for a specific reason

Key secondary outcomes

(1) Progression-free rate (24 weeks and 48 weeks): Percentage of cases of CR, PR, and SD. (However, when CR and PR keep the same condition for more than 4 weeks)
(2) Maximum Standarized Uptake Value (SUV) change rate by FDG-PET
(3) Evaluation of affected limb function (baseline, 24 weeks, 48 weeks): The Japanese Orthopedic Association score, MSTS score
(4) Percentage of cases in which clinical benefit about pain, range of motion of joint, joint function compared with baseline is observed at 24 weeks and 48 weeks (judgment by investigator or clinical trial physician)
(5) Types, incidence and severity of adverse events and abnormal laboratory data (graded using CTCAE v4.0), The severity and the relationship with the investigational drug will be evaluated

Base

Study type

Interventional

Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

YES

Concealment

Central registration

Intervention

No. of arms

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

In the zaltoprofen group, 2 tablets of zaltoprofen (80 mg) 3 times a day, 2 placebo tablets in placebo group orally 3 times a day with water of 1 cup or more (about 150 mL) or more after oral administration .
Gastric mucosa protective agent is orally administered in regular dosage and dose as a concomitant medicine.

Interventions/Control_2

48 weeks administration

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Eligibility

Age-lower limit

20 years-old <=

Age-upper limit

70 years-old >=

Gender

Male and Female

Key inclusion criteria

Patients who satisfy all of the following conditions are included.
(1) Patients who sufficiently are explained the research purpose, interests and disadvantages before starting the examination about the clinical trial, understand it, and obtained written informed consent. No substitute is allowed.
(2) Patients who are diagnosed as diffuse type tendinous synovial giant cell tumor (pigmented chorionic synovitis) or unresectable localized tendonous synovial giant cell tumor occurred in the knee joint or ankle by radiological findings and pathological findings
(3) Patient with measurable lesion based on RECISTv 1.1 with at least one knee joint or ankle joint.
(4) Patients who keep joint space in the knee joint or ankle joint in standing X-ray imaging.
(5) Patients aged 20 years or older and under 70 years old at the time of acquisition.
(6) In the case of a pregnant woman, a patient whose pregnancy test to be conducted during the screening period is negative.

Key exclusion criteria

The following patients must be excluded.
(1) Patients with severe heart disease, renal disease, respiratory disease, blood disease, diabetes, coagulopathy, hepatic injury, renal disorder
(2) Patients with gastlic ulcer.
(3) Patient with aspirin asthma or a history of aspirin.
(4) Patients who have had a history of allergic symptoms such as itching and rash, taking zaltoprofen (Soleton tablet 80, Peon tablet 80 etc) before.
(5) Hypersensitivity to additives of zaltoprofen (lactose hydrate, corn starch, cellulose, silicic anhydride, hydroxypropyl cellulose, carmellose Ca, stearic acid Mg, polysorbate 80, hypromellose, titanium oxide, talc, carnauba wax) Patient with a history of disease.
(6) Patients who are administered any of the following agents within 14 days prior to enrollment: tyrosine kinase inhibitors, nonsteroidal anti-inflammatory drugs, thiazolidine derivatives and drug with thiazolysine ring
(7) Patients who have a limited active range of motion more than 20% with respect to the healthy side
(8) Patients whose joint space has disappeared by standing position X-ray photography.
(9) Patients who are inappropriate for MRI, PET, etc. examination.
(10) Patients who are pregnant or lactating. Or patients who do not agree to contraception from the final administration of the study drug to 90 days after.
(11) Patients who are difficult to take oral medicine.
(12) Patients who were using other investigational drugs or using the investigational device within 3 months prior to the study drug administration.
(13) A patient whose investigator or clinical trial doctor judged unsuitable for participation in this trial due to other reasons.

Target sample size

Research contact person

Name of lead principal investigator

1st name Hiroyuki

Middle name

Last name Tsuchiya

Organization

Kanazawa University Hospital

Division name

Orthopaedic surgery

Zip code

9208641

Address

13-1 Takaramachi, Kanazawa, Japan

TEL

076-265-2000

Email

tsuchi@med.kanazawa-u.ac.jp

Public contact

Name of contact person

1st name Akihiko

Middle name

Last name Takeuchi

Organization

Kanazawa University

Division name

Orthopaedic Surgery

Zip code

920-8641

Address

13-1 Takaramachi, Kanazawa, Japan

TEL

076-265-2000

Homepage URL

Email

a_take@med.kanazawa-u.ac.jp

Sponsor or person

Institute

Kanazawa University

Institute

Department

Personal name

Funding Source

Organization

Japan Agency for Medical Research and Developmen

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Other related organizations

Name of secondary funder(s)

IRB Contact (For public release)

Organization

Kanazawa University Hospital Research Review Committee

Address

13-1 Takaramachi, Kanazawa, Japan

Tel

076-265-2000

Email

crc.irb-knz@esct.jp

Secondary IDs

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Other administrative information

Date of disclosure of the study information

2017 Year 04 Month 01 Day

Related information

URL releasing protocol

https://www.frontiersin.org/articles/10.3389/fonc.2022.900010/full

Publication of results

Published

Result

URL related to results and publications

https://www.frontiersin.org/articles/10.3389/fonc.2022.900010/full

Number of participants that the trial has enrolled

Results

Forty-one patients were allocated to the zaltoprofen (n=21) or placebo (n=20) groups. The PFR was not significant between the zaltoprofen group and the placebo group at 48 weeks. The mean Japanese Orthopedic Association knee score significantly improved from baseline to week 48 in the zaltoprofen group. There was a significant difference between the values at 48 weeks of placebo and zaltoprofen group. One severe adverse event (grade 3 hypertension) was observed in the zaltoprofen group.

Results date posted

2023 Year 01 Month 12 Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2022 Year 09 Month 22 Day

Baseline Characteristics

https://www.frontiersin.org/articles/10.3389/fonc.2022.900010/full

Participant flow

https://www.frontiersin.org/articles/10.3389/fonc.2022.900010/full

Adverse events

https://www.frontiersin.org/articles/10.3389/fonc.2022.900010/full

Outcome measures

https://www.frontiersin.org/articles/10.3389/fonc.2022.900010/full

Plan to share IPD

IPD sharing Plan description

Progress

Recruitment status

Completed

Date of protocol fixation

2017 Year 01 Month 22 Day

Date of IRB

2017 Year 02 Month 08 Day

Anticipated trial start date

2017 Year 04 Month 04 Day

Last follow-up date

2020 Year 06 Month 30 Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other

Other related information

Management information

Registered date

2017 Year 01 Month 30 Day

Last modified on

2023 Year 01 Month 12 Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029596

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name