UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000016305
Receipt number R000018342
Scientific Title Multicentric feasibility study for the combination of dose-dense cisplatin and surgical therapies for high-risk hepatoblastoma (JPLT3-H)
Date of disclosure of the study information 2015/01/25
Last modified on 2022/04/13 10:46:26

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Basic information

Public title

Multicentric feasibility study for the combination of dose-dense cisplatin and surgical therapies for high-risk hepatoblastoma (JPLT3-H)

Acronym

Dose-dense cisplatin therapy for high-risk hepatoblastoma

Scientific Title

Multicentric feasibility study for the combination of dose-dense cisplatin and surgical therapies for high-risk hepatoblastoma (JPLT3-H)

Scientific Title:Acronym

Dose-dense cisplatin therapy for high-risk hepatoblastoma

Region

Japan


Condition

Condition

Hepatoblastoma with distant metastasis at diagnosis (high-risk hepatoblastoma)1

Classification by specialty

Gastrointestinal surgery Pediatrics

Classification by malignancy

Malignancy

Genomic information

YES


Objectives

Narrative objectives1

This trial is part of the third generation of clinical trials run by the JPLT group. Hepatoblastoma is the most common malignant liver neoplasm in children but this incidence is rare(approximately one by several ten thousands children a year).Therefore, 30-40 cases were registered to JPLT a year. To identify the new effective regimen, nationwide clinical trials are needed. JPLT was launched at 1991 and preformed JPLT1 and JPLT2 protocols. Although surgical resection is the main strategy of curative therapy for children with hepatoblastoma, only one-third to one-half of newly diagnosed patients with hepatoblastoma can be expected to have resectable disease at presentation. Outcome of the patients with distant metastasis at diagnosis (high risk hepatoblastom) remain poor. In 2013, SIOPEL group (Europe) showed the efficacy of high dose cisplatin therapy for such cases. In this JPLT3 study, we are willing to conform the feasibility of this high dose-dense cisplatin therapy in high risk hepatoblastoma patient for the next- international collaboration study.

Basic objectives2

Safety

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase

Phase I,II


Assessment

Primary outcomes

Toxicities and these percentage

Key secondary outcomes

Remission rate at the end of therapy
Response rate of pre-operative chemotherapy
Percentage of surgical complications
Accomplishment rate
Pathohistological evaluation of preoerative chemothearapy
genetic analysis(cases with approval)
banking (cases with approval)


Base

Study type

Interventional


Study design

Basic design

Single arm

Randomization

Non-randomized

Randomization unit


Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

NO

Dynamic allocation

NO

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

YES

Concealment

No need to know


Intervention

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

According to SIOPEL4 protocol, after administration of preoperative chemotherapy consisting of 3 blocks chemotherapy of weekly cisplatin (CDDP) and doxorubicin (DOX), surgical resection is performed and then postsurgical chemotherapy is administrated. If the complete resection using liver transplantation is impossible after 3 block preoperative chemotherapy, additional chemotherapy consisting carboplatin and DOX is performed.

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

18 years-old >

Gender

Male and Female

Key inclusion criteria

1) Histologically confirmed newly diagnosed hepatoblastoma or Primary liver tumor with high levels of serum AFP
2) high risk hepatoblastoma: by international risk stratification
3) any PRETEXT with M1 (distant metastasis) or N2 (distant lymph-node metastasis)
4) or Serum alpha-fetoprotein (AFP) < 100 ng/ml
5) Definition of lung metastasis: one nodule is larger than 1 cm or several nodules with one lesion ( > 5mm)
6) Age <= 18 years and >=1 month
7) No previous chemotherapy, surgery, radiotherapy for this disease
8) Written informed consent and national/local ethics committee and regulatory approval
9) Ability to comply with requirements for submission of material for central review (radiology, pathology and biology)
10) No severe organ failure: the cases who will be alive for more than 3 months
1PS: Karnofsky/Lansky performance status>30
2White cell counts > 2000/micro L
3ALT <= 300IU/L and T.Bil < 2.0 mg/dl
But, the cases whose total bilirubin levels increased by physiological (constitutional or neonatal) icterus are excluded.
4Creatinine clearance by 24 hours urine or estimated GFR calculated by Schwartz formula > 70mL/min/1.73 m2
5No cardiac diseases requiring treatments
11) No active infections
12) Female patients of childbearing potential are not eligible unless a negative pregnancy text result has been obtained
13) Females of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method

Key exclusion criteria

Cases with one or more following factors
1) rhabdoid tumor
2) Hepatocellular carcinoma
3) Treatments was started at more than 15 days after the report of biopsy or
4) Cases who will be unable to be alive for more than 3 months
5) Abnormal renal function defined as GFR < 50% of the lower limit of normal for age, which over 2 years of age is < 70 ml/min/1.73 m2 at diagnosis
6) Abnormal heart function (initial EF < 50% or SF < 28%)
7) Active double cancers
8) Recurrent diseases
9) Female under pregnancy
10) Patient unable to undergo chemotherapy by poor general condition, complications or abnormalities
11) Case whose approval to register this trail is refused
12) Patients unable to the protocol for any reasons


Target sample size

15


Research contact person

Name of lead principal investigator

1st name Eiso
Middle name
Last name Hiyama

Organization

Hiroshima University

Division name

Natural Science Center for Basic Reseach and Development

Zip code

734-8551

Address

1-2-3, Kasumi, Minami-ku, Hiroshima

TEL

082-257-5951

Email

eiso@hiroshima-u.ac.jp


Public contact

Name of contact person

1st name Sho
Middle name
Last name Kurihara

Organization

Hiroshima University Hospital

Division name

Pediatric Surgery

Zip code

7348551

Address

1-2-3, Kasumi, Minami-ku, Hiroshima

TEL

082-257-5951

Homepage URL

http://home.hiroshima-u.ac.jp/eiso/index.html

Email

jplt@hiroshima-u.ac.jp


Sponsor or person

Institute

Japanese Study Group for Pediatiric Liver Tumor (JPLT)

Institute

Department

Personal name



Funding Source

Organization

Grants-in-aid for Scientific Research, Ministry for Health, labour, and Welfare

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor

Grants-in-aid for Scientific Research, Ministry for Education, Culture, Sports, Science and technology-JAPAN

Name of secondary funder(s)



IRB Contact (For public release)

Organization

HIROSHIMA UNIVERSITY

Address

1-2-3, Kasumi, Minami-ku, Hiroshima, JAPAN

Tel

+81822575555

Email

https://ethics.hiroshima-u.ac.j


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

広島大学病院(広島県)他20施設


Other administrative information

Date of disclosure of the study information

2015 Year 01 Month 25 Day


Related information

URL releasing protocol

http://home.hiroshima-u.ac.jp/eiso/

Publication of results

Published


Result

URL related to results and publications

https://home.hiroshima-u.ac.jp/eiso/

Number of participants that the trial has enrolled

15

Results

Until September 30, 2018, 15 cases were enrolled.

Results date posted

2022 Year 04 Month 13 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results

2021 Year 10 Month 04 Day

Baseline Characteristics

Patients with primary histologically confirmed hepatoblastoma occurring at age 1 month or older and aged 18 years or younger who are at high risk according to the following international common classification
PRETEXT additional factors
M1
N2
Serum alpha-fetoprotein (hereafter serum AFP) <100 ng/ml

Participant flow

Central review of pathology slides by biopsy and central diagnosis of radiological images as a principle in all cases.
Participation after diagnosis of high-risk hepatoblastoma.

Adverse events

Anticipated Adverse Events from Chemotherapy
Myelosuppression such as acute renal failure, pancytopenia, shock, anaphylactoid symptoms, hearing loss/deafness, tinnitus, congestive papilla, retrocortical optic neuritis, blind cortex, cerebral infarction, transient ischemic attack, hemolytic uremic syndrome, myocardial infarction, angina pectoris, congestive heart failure, arrhythmia, hemolytic anemia, interstitial pneumonia, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), fulminant hepatitis, hepatic dysfunction, jaundice, gastrointestinal hemorrhage, gastrointestinal ulcer, gastrointestinal perforation, acute pancreatitis, hyperglycemia, aggravation of diabetes mellitus, rhabdomyolysis, leukoencephalopathy,
Alopecia, nausea/vomiting, ileus, diarrhea, stomatitis, liver dysfunction, electrolyte abnormalities, peripheral neuropathy, convulsion, consciousness disorder, myocardial disorder, heart failure, electrocardiogram abnormalities, palpitations, tachycardia, chest pain, proteinuria, pigmentation, headache, reverse smoking, hypotension, hyperuricemia, dehydration, Raynaud's-like symptoms
Anticipated Adverse Events from Surgical Resection
Dysfunction of surgical site, bleeding, organ injury, combined resection, hypotension, hypertension, ventilatory disturbance, apnea, malignant hyperthermia, hypothermia, atelectasis, vomiting/aspiration, excessive transfusion, undertransfusion, wound infection, ileus, postoperative bleeding, gastrointestinal fistula, gastrointestinal perforation, hematoma, pain, hydronephros/hydroureter, and nonfunctioning kidney

Outcome measures

Primary Endpoint: Protocol Completion Rate
Secondary endpoint :
End-of-treatment remission rate
Treatment response to neoadjuvant chemotherapy
Rate of complete resections
Surgical complication rate
Histopathological evaluation after neoadjuvant chemotherapy

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2014 Year 12 Month 15 Day

Date of IRB

2019 Year 01 Month 30 Day

Anticipated trial start date

2015 Year 01 Month 01 Day

Last follow-up date

2019 Year 03 Month 31 Day

Date of closure to data entry

2022 Year 03 Month 31 Day

Date trial data considered complete

2022 Year 12 Month 31 Day

Date analysis concluded

2023 Year 03 Month 31 Day


Other

Other related information



Management information

Registered date

2015 Year 01 Month 22 Day

Last modified on

2022 Year 04 Month 13 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018342


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name