UMIN-CTR Clinical Trial

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

advanced and recurrent neuroblastoma

Classification by specialty

Pediatrics

Classification by malignancy

Malignancy

Genomic information

NO

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

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

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

National Cancer Research Center
Hospital
Division of Pediatric Oncology

Institute

Department

Personal name

Organization

National Cancer Research Center
Hospital

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

National cacncer center

Name of secondary funder(s)

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

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立がん研究センター中央病院

Date of disclosure of the study information

2013

Year

05

Month

29

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

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 related information

Registered date

2013

Year

05

Month

29

Day

Last modified on

2020

Year

02

Month

04

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012687