UMIN-CTR Clinical Trial

Basic information
Public title	Efficacy and safety of Targretin capsule 75-mg alone or in combination with phototherapy in Japanese patients with Cutaneous T-cell Lymphomas
Acronym	Efficacy and safety of bexarotene or bexarotene plus phototherapy in CTCL
Scientific Title	Efficacy and safety of Targretin capsule 75-mg alone or in combination with phototherapy in Japanese patients with Cutaneous T-cell Lymphomas
Scientific Title:Acronym	Efficacy and safety of bexarotene or bexarotene plus phototherapy in CTCL
Region	Japan

Condition
Condition	Cutaneous T-Cell Lymphomas
Classification by specialty	Dermatology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To assess the efficacy and safety of bexarotene alone or bexarotene plus phototherapy for cutaneous T-cell lymphoma patients
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	The primary efficacy endopoints evaluated though the 8 weeks of treatment were follows: Modified Severity-weighted Assessment Tool (mSWAT), Physician's Global Assessment (PGA)
Key secondary outcomes	Efficacy: time to cutaneous tumor response, time to cutaneous tumor progression, amount of irradiation and UV dose, amount of bexarotene, capsules, and compliance rate, LDH, sIL-2R, TARC, T-cell receptor repertoire analysis Safety: adverse events, hematology, blood chemistry

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is considered as adjustment factor in dynamic allocation.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine Device,equipment
Interventions/Control_1	Patients are p.o. administrated a 300 mg/m2 dose of bexarotene once daily for 8 weeks.
Interventions/Control_2	Patients are p.o. administrated a 300 mg/m2 dose of bexarotene once daily for 8 weeks. Patients are treated with psoralen baths preceding treatment with UVA radiation 5 times weekly. The initial dose of UVA was 0.5 J/cm2, dose increment of 0.5 J/cm2 each radiation. The maximum dose was 4.0 J/cm2. The initial dose of narrowband UVB administered is 50-70% of the MPD or 0.5-0.7 J/cm2. The dose of NB-UVB for the subsequent NB-UVB sessions is elevated 20% increments with each successive treatment session. The maximum dose is 2.0 J/cm2.
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	Not applicable
Gender	Male and Female
Key inclusion criteria	Subjects must have met all of the following inclusion criteria: 1. A clinical diagnosis of cutaneous T-cell lymphomas confirmed by biopsy to be histologically consistent with CTCL diagnosis by dermatopathologist 2. Age >= 20, written approval of patient
Key exclusion criteria	1. Contraindications (severe liver failure, known hypersensitivity to bexarotene, systemic therapy with vitamin A or oral retinoid therapy at the entry in this study, hypervitaminosis A) 2. Patients with pregnancy, breast-feeding or intent to become pregnant 3. Skin-directed therapies, local chemotherapy, topical steroids, etc. within 2 weeks of study entry. Low- and mid-potency topical corticosteroids were allowed only for subjects using a stable dose regimen at least 2 weeks prior to study entry. High potency topical corticosteroids were not allowed permitted. 4. Prior therapy for the treatment of CTCL: therapy with UVA or UBV within 3 weeks of study entry 5. Prior therapy for the treatment of CTCL: radiotherapy within 4 weeks of study entry 6. Prior therapy for the treatment of CTCL: therapy with bexarotene within4 weeks of study entry 7. Known allergic reaction or hypersensitivity to bexarotene or other component of Targretin capsules 8. History of severe allergic reaction or hypersensitivity to any other drugs or prior therapy for the treatment of CTCL 9. Unwillingness or inability to minimize exposure to sunlight and antificial UV light while receiving bexarotene 10. Principal investigator or subinvestigator judged inadequate
Target sample size	60

Research contact person
Name of lead principal investigator	1st name Akimichi Middle name Last name Morita
Organization	Nagoya City University Graduate School of Medical Sciences
Division name	Department of Geriatric and Environmental Dermatology
Zip code	4678601
Address	1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi
TEL	052-853-8261
Email	amorita@med.nagoya-cu.ac.jp

Public contact
Name of contact person	1st name Akimichi Middle name Last name Morita
Organization	Nagoya City University Graduate School of Medical Sciences
Division name	Department of Geriatric and Environmental Dermatology
Zip code	4678601
Address	1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi
TEL	052-853-8261
Homepage URL
Email	amorita@med.nagoya-cu.ac.jp

Sponsor
Institute	Nagoya City University Graduate School of Medical Sciences Department of Geriatric and Environmental Dermatology
Institute
Department

Funding Source
Organization	Minophagen Pharmaceutical Co., Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor	Osaka City University Graduate School of Medicine
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Nagoya City University Graduate School of Medical Sciences and Nagoya City University Hospital Institutional Review Board
Address	1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi
Tel	0528587215
Email	clinical_research@med.nagoya-cu.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	名古屋市立大学，大阪市立大学

Other administrative information
Date of disclosure of the study information	2017 Year 10 Month 16 Day

Related information
URL releasing protocol	https://jrct.niph.go.jp/search?page=1
Publication of results	Published

Result
URL related to results and publications	https://jrct.niph.go.jp/search?page=1
Number of participants that the trial has enrolled	53
Results	We conducted the comparative study on the efficacy and safety between the Targretin monotherapy and the Targretin/phototherapy combination therapy for CTCL. In the efficacy, no difference was observed in the therapeutic effect of the two therapies evaluated by mSWAT and PGA at 8 weeks, but the two therapies have been shown to have therapeutic effects. In the combination therapy, 4 subjects were diagnosed to be the complete response, and it was suggested that the combination therapy may have a high effect.
Results date posted	2021 Year 05 Month 10 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	A total of 46 subjects (29 males and 17 females) were enrolled, and 7 subjects were excluded. Twenty-four subjects (15 males and 9 females) and 22 subjects (14 males and 8 females) were assigned to the Targretin monotherapy group and the Targretin + phototherapy combination therapy group, respectively. The mean age was 69.3 years. The mean duration of cutaneous T-cell lymphoma (CTCL) was 2.06 years. No significant difference was observed between the two groups in terms of CTCL type or any other baseline characteristics.
Participant flow	Registration period: between September 2017 and September 2019 Number of patients enrolled: November 2017; 1, December 2017; 4, January 2018; 1, February 2018; 4, April 2018; 2, May 2018; 2, June 2018; 1, July 2018; 3, August 2018; 2, September 2018; 1, October 2018; 4, November 2018; 3, January 2019; 1, February 2019; 1, March 2019; 2, May 2019; 1, June 2019; 1, July 2019; 4, August 2019; 4, September 2019; 4
Adverse events	The adverse events (AEs) that were reported during the research treatment and follow-up period of this study were 120 cases in 24 subjects of the Targretin monotherapy group and 111 cases in 22 subjects of the Targretin + phototherapy combination therapy group, respectively. Of the AEs, 5 serious adverse events were reported in 5 subjects, respectively (hypertriglyceridemia, type 2 diabetes, acute cholecystitis, rhabdomyolysis and interstitial lung disease). In addition, adverse drug reaction were also reported in 87 cases in 24 subjects of the Targretin monotherapy group and 77 cases in 22 subjects of the Targretin + phototherapy combination therapy group, respectively. The serious adverse drug reactions were reported in 3 cases in 3 subjects, respectively (hypertriglyceridemia, rhabdomyolysis and interstitial lung disease).
Outcome measures	No significant difference was observed between the two groups in the response rate by mSWAT evaluation or any the PGA evaluation after 8 weeks, which are the primary endpoints of this study. No difference was observed between the groups regarding the time to response period based on the mSWAT evaluation, which was a secondary endpoint. In both the groups, mSWAT scores were decreased over time until the time of evaluation at 8 weeks, indicating a therapeutic effect on CTCL. In the mSWAT evaluation, the rate of the decreases from baseline at 8 weeks tended to be greater in the Targretin + phototherapy combination therapy group. There was a difference in the rate of change in mSWAT between the research institutions. In Nagoya City University Hospital, the decrease from baseline was observed in both the groups. However, in Osaka City University Hospital, but the decrease was not observed in any of the groups.
Plan to share IPD	none
IPD sharing Plan description	none

Progress
Recruitment status	Completed
Date of protocol fixation	2017 Year 09 Month 11 Day
Date of IRB	2017 Year 09 Month 11 Day
Anticipated trial start date	2017 Year 10 Month 16 Day
Last follow-up date	2019 Year 12 Month 26 Day
Date of closure to data entry	2020 Year 03 Month 31 Day
Date trial data considered complete	2020 Year 06 Month 05 Day
Date analysis concluded	2020 Year 10 Month 31 Day

Other
Other related information

Management information
Registered date	2017 Year 10 Month 13 Day
Last modified on	2021 Year 05 Month 10 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000033748