UMIN-CTR Clinical Trial

Basic information
Public title	Phase Ib study of Valproic Acid (VPA) and 13-cis-RA(isotretinoin) combination therapy for advanced and recurrent neuroblastoma.
Acronym	Phase Ib of VPA + 13-cis-RA for advanced and reccurent neuroblastoma.
Scientific Title	Phase Ib study of Valproic Acid (VPA) and 13-cis-RA(isotretinoin) combination therapy for advanced and recurrent neuroblastoma.
Scientific Title:Acronym	Phase Ib of VPA + 13-cis-RA for advanced and reccurent neuroblastoma.
Region	Japan

Condition
Condition	advanced and recurrent neuroblastoma
Classification by specialty	Pediatrics
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To evaluate pharmacokinetics, pharmacodynamics study and feasibility of the Valproic acid (VPA) as histon deacerylase(HDAC) inhibitor combined with differentiation-inducing therapy by 13-cis RA(isotretinoin).
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase I

Assessment
Primary outcomes	MTD(maximum tolerated dose)
Key secondary outcomes	DLT(Identification and generating rate) Adverse events profile VPA(target serum concentration ) Response rate Progression free survival Overall survival Proportion of the patients who complete all six courses for all registered. Pharmacokinetics

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Fourteen-days oral administration of 13-cis RA every 28 days repeated up to 6 cycles, and concurrent with daily administration of VPA orally to maintained the target concentration.
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

Eligibility
Age-lower limit	1 years-old <=
Age-upper limit	30 years-old >=
Gender	Male and Female
Key inclusion criteria	1.neuroblastoma(historical) 2.The following status of patients completing standard treatment a. Recurrence, after 2nd-line chemotherapy. b. Stage2 or 3 with residual disease c. Stage4 3. Prior history of autologous hematopoietic stem cell transplantation. 4. No prior history of allogeneic hematopoietic stem cell transplantation. 5. More than 7 days after chemotherapy which has hematological DLT. 6. More than 7 days after chemotherapy which has non-hematological DLT 7. More than 21 days after radiation therapy 8.More than 14 days after surgery 9.More than 14 days after 13-cis-RA 10. More than 7 days after erythrocyte or platelet transfusion 11.PS>=50% 12.Any organ function is maintained. 13.No oxygen demand is needed 14.no difficulty to take 15mm capsule. 15.legal adult:written informed consent. 16.16 years and over,but, no legal adult: written informed consent from both patient and legal guardian. 17.15 years and under: written informed consent from legal guardian.
Key exclusion criteria	1. active double cancer(synchronous double cancer and metachronous double cancer within 5 disease -free years),excluding carcinoma In situ(lesions equal to Intraepithelial or intramucosal Cancer)judged to have been cured with local treatment. 2. active infection requiring systemic medication. 3. abnormality in electrocardiogram tested within 28 days,requiring intervention. 4. respiratory or heart disorder requiring oxygen supply,except from malignant pleural effusion. 5. women during pregnancy or breast-feeding. 6. Psychosis.
Target sample size	15

Research contact person
Name of lead principal investigator	1st name Hiroshi Middle name Last name Kawamoto
Organization	National Cancer Research Center Hospital
Division name	Division of Pediatric Oncology
Zip code	104-0045
Address	5-1-1 Tsukiji,Chuo-ku,Tokyo
TEL	03-3542-2511
Email	ped-dev@ml.res.ncc.go.jp

Public contact
Name of contact person	1st name Naoko Middle name Last name Yasui
Organization	National Cancer Research Center
Division name	Division of Pediatric Oncology
Zip code	104-0045
Address	5-1-1 Tsukiji,Chuo-ku,Tokyo, Japan.
TEL	03-3542-2511
Homepage URL
Email	nyasui@ncc.go.jp

Sponsor
Institute	National Cancer Research Center Hospital Division of Pediatric Oncology
Institute
Department

Funding Source
Organization	National Cancer Research Center Hospital
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	National cacncer center
Name of secondary funder(s)

IRB Contact (For public release)
Organization	National Cancer Center
Address	5-1-1, Tsukiji, Chuo-ku, Tokyo
Tel	03-3542-2511
Email	ped-dev@ml.res.ncc.go.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	国立がん研究センター中央病院

Other administrative information
Date of disclosure of the study information	2013 Year 05 Month 29 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 04 Month 05 Day
Date of IRB	2013 Year 04 Month 30 Day
Anticipated trial start date	2013 Year 05 Month 29 Day
Last follow-up date	2016 Year 03 Month 03 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2013 Year 05 Month 29 Day
Last modified on	2020 Year 02 Month 04 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012687