UMIN-CTR Clinical Trial

Basic information
Public title	Phase Ib study of 131I-metaiodobenzylguanidine(MIBG) therapy with Valproic Acid(VPA) for high risk or recurrent neuroblastoma
Acronym	Phase Ib study of VPA and 131I-MIBG for recurrent / resistant neuroblastoma
Scientific Title	Phase Ib study of 131I-metaiodobenzylguanidine(MIBG) therapy with Valproic Acid(VPA) for high risk or recurrent neuroblastoma
Scientific Title:Acronym	Phase Ib study of VPA and 131I-MIBG for recurrent / resistant neuroblastoma
Region	Japan

Condition
Condition	Intractable neuroblastoma
Classification by specialty	Pediatrics
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	To investigate whether 131I-MIBG with concurrent VPA, a histon deacerylase (HDAC) inhibitory drug, administration can be completed safely without hematopoetic stem cell rescue
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Explanatory
Developmental phase	Phase I

Assessment
Primary outcomes	Proportion of patients who can recover at normal hematologic status without hematopoetic stem cell rescue
Key secondary outcomes	DLT(profile and incidence) Adverse events profile Proportion of patients maintaining target serum concentration of VPA Clinical benefit rate Response rate identification of problem and solution for perform 131I-MIBG therapy

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	(1) After enrollment, starting valproic acid (VPA) and adjusting VPA dosing to reach and keep the target concentration (100ug/ml). (2) Preparing for 131I-MIBG administration by assessing disease status (123I-MIBG, Bone marrow biopsy etc.) and training for staying alone in isolated room (3) After second admission, 131I-MIBG 12 mCi/kg is infused intravenously, concurrently using KI and perchlorate potassium for protecting thyroid. (4) outpatient ward management after confirming fall of radiation dose from body. (5) G-CSF s.c. or reserved stem cell transplantation infusion according patient's hematologic status.
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	3 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. histological proven neuroblastoma 2. ability to control urination and body weight = < 18kg 3. PS (Lansky) >= 50% 4. any radiologically confirmed residual disease which are not shrinking or any tumor associated symptoms, despite prior chemotherapies 5. any diseases evaluable by 123I-MIBG scan performed within 8 weeks 6. any non-irradiated disease with 123I-MIBG uptake which compress spinal cord 7. autologous hematopoietic stem cell product available for re-infusion after MIBG treatment whose quantity is more than 1.5*10^6 CD34+ cells/kg or 1.0*10^6 CD34+ cells/kg if the quality is confirmed within 8 weeks. 8. If the last chemotherapy contains one or more drugs with hematologic dose limiting toxicity (DLT), 7 days or more have passed since last use of anti-tumor agents which are administerd protractedly and 14 days or more have passed since last use of anti-tumor agents which are not administered in protracted way 9.7 days or more have passed since the anti-cancer drug (dosage restriction toxicity is non-hematologic toxicity) 10. No prior irradiation within 14 days if radiation fields is limited. No prior irradiation within 3 months if radiation fields contain either whole brain and spine, whole abdomen, whole lung, whole body, or more than 50% of pelvis. No prior irradiation within 6 weeks if radiation fields contain either less than 50% of pelvis, or 5 or less vertebras. 11. No oral 13-cis-RA within 14 days. 12 Any red blood cell (RCC) transfusion or platlet cell (PC) transfusion history within 7 days from registration or the last RCC or PC transfusion. 13. Normal organ function confirmed by laboratory tests within 14 days 14. No exertional dyspnea and no oxygen supply for everyday life. 15. No need for any anti-epileptics, phycotropics or anti-hypertentsivesexcept VPA during treatment. 16. Written informed consent from patient and/or 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. Psychosis which is not appropriate for participating in this study
Target sample size	10

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 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
Homepage URL
Email	ped-dev@ml.res.ncc.go.jp

Sponsor
Institute	National Cancer Research Center Hospital
Institute
Department

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

Other related organizations
Co-sponsor
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	NCC_IRBoffice@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（東京都）

Other administrative information
Date of disclosure of the study information	2013 Year 10 Month 14 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 01 Day
Date of IRB	2013 Year 09 Month 30 Day
Anticipated trial start date	2013 Year 10 Month 15 Day
Last follow-up date	2015 Year 07 Month 14 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 10 Month 14 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=R000014062