UMIN-CTR Clinical Trial

Public title

Prospective study of I-131 3-iodobenzylguanidine radiotherapy for refractory pheochromocytoma; in accordance with the Japanese Advanced Medical Care B program for the anticancer drug with high medical needs.

Acronym

Prospective study of I-131 3-iodobenzylguanidine radiotherapy for refractory pheochromocytoma; in accordance with the Japanese Advanced Medical Care B program for the anticancer drug with high medical needs.

Scientific Title

Prospective study of I-131 3-iodobenzylguanidine radiotherapy for refractory pheochromocytoma; in accordance with the Japanese Advanced Medical Care B program for the anticancer drug with high medical needs.

Scientific Title:Acronym

Prospective study of I-131 3-iodobenzylguanidine radiotherapy for refractory pheochromocytoma; in accordance with the Japanese Advanced Medical Care B program for the anticancer drug with high medical needs.

Region

Japan

Condition

Refractory pheochromocytoma (including paraganglioma)

Classification by specialty

Endocrinology and Metabolism	Endocrine surgery	Urology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The aim of this study is to evaluate the safety and the efficacy of I-131 3-iodobenzylguanidine (I-131 MIBG) radiotherapy for I-123 MIBG-avid refractory pheochromocytoma, along with the following primary and secondary endpoints. Additionally, this study was performed in accordance with the Japanese Advanced Medical Care B program ahead to sponsor initiated clinical trial, which intend to rationalize application for approval under the Japanese Pharmaceutical and Medical Device Act.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Dose limiting toxicity (DLT)

Key secondary outcomes

Types and frequency of adverse event/reaction
Response rate under the RECIST criteria
Response rate under scintigraphic evaluation of MIBG
Overall survival (OS)
Progression-free survival (PFS)

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

I-131 3-iodobenzylguanidine (I-131 MIBG) radiotherapy

Administering the radiopharmaceutical in accordance with the following regimen every 24 weeks until satisfying withdrawal or dose-reduction criteria.
Radiopharmaceutical: 131I-MIBG
Dose: 7,400MBq (=200mCi)* i.v. in 1 hour
*Administering maximal dose of permitted amount of radioisotopes in each facility, if permitted amount is lower than 7,400MBq.

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

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Satisfying all the following conditions.
1)Confirmed pheochromocytoma, paraganglioma, malignant pheochromocytoma, or malignant paraganglioma.
2)Not applicable any kind of surgical treatment and radical external irradiation.
3)I-123 MIBG-avid tumor.
4)Satisfying each condition:
4)-1 WBC >= 3,000[/mm3], Hb >= 9.0[g/dL] and platelets >= 100,000[/mm3] under G-CSF non-administraion.
4)-2 eGFR >= 30[mL/min/1.73m2]
4)-3 AST < 100[IU/L], ALT < 100[IU/L] and LDH < 400[IU/L]
4)-4 New York Heart Association (NYHA) Functional Classification class I or below.
4)-5 HbA1c < 8.0%
4)-6 Oxygen saturation >= 96[%] at room air.
5)Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2 and Karnofsky Performance Scale (KPS) 80[%] or more.
6)Age 20 or older.
7)Independent feeding, excretion and sleeping.
8)Written consent to participate in this study and treatment.

Key exclusion criteria

Satisfying any of the following conditions.
1)Previous or current malignancies of other histologies within the last 5 years.
2)History of tumor deterioration under the condition of I-131 MIBG radiotherapy before this study.
3)History of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more in non-hematotoxicity, or grade 3 or more in hematotoxicity under the condition of I-131 MIBG radiotherapy before this study.
4)CTCAE grade 2 or more toxicity currently treated under the condition of any kind of anticancer treatments before this study.
5)Diagnosed as Hepatitis B virus, Hepatitis C virus, Human Immunodeficiency virus (HIV) or any other infections currently treated.
6)Episodes of severe symptoms due to uncontrollable increase of catecholamines.
7)Episodes of fatal arrhythmia or asystole.
8)Diagnosed as any of the following diseases or conditions out of control.
8)-1 symptomatic arrhythmia
8)-2 thyroid dysfunction (hyperthyroidism or hypothyroidism)
8)-3 respiratory disease
8)-4 pleural effusion or ascites
9)Diagnosed as any of the following disease or conditions.
9)-1 coronary artery disease
9)-2 administration of amiodarone
9)-3 severe valvular disease of the heart
9)-4 aortic disease
9)-5 bleeding disorder
10)Pregnant or lactating women, or desire to bear children.
11)Diagnosed as psychosis.
12)Diagnosed as any diseases currently treated with adrenal corticosteroids or immunosuppressants.
13)Not applicable isolation due to radiation control.
14)Episodes of allergic reaction to potassium iodide.
15)Any symptomatic lesions currently treated with palliative external irradiation.

Target sample size

20

Name of lead principal investigator

1st name	Seigo
Middle name
Last name	Kinuya

Organization

Kanazawa University

Division name

Institute of Medical, Pharmaceutical and Health Sciences

Zip code

920-8641

Address

13-1, Takara-machi, Kanazawa

TEL

076-265-2333

Email

kinuya@med.kanazawa-u.ac.jp

Name of contact person

1st name	Anri
Middle name
Last name	Inaki

Organization

Kanazawa University

Division name

Institute of Medical, Pharmaceutical and Health Sciences

Zip code

920-8641

Address

13-1, Takara-machi, Kanazawa

TEL

076-265-2333

Homepage URL

Email

henri@staff.kanazawa-u.ac.jp

Institute

Kanazawa University

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Innovative Clinical Research Center, Kanazawa University

Address

13-1, Takara-machi, Kanazawa

Tel

076-265-2090

Email

crc.irb-knz@esct.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

金沢大学附属病院（石川県）
鹿児島大学病院（鹿児島県）
北海道大学病院（北海道）
群馬大学医学部附属病院（群馬県）

Date of disclosure of the study information

2015

Year

07

Month

31

Day

URL releasing protocol

https://www.jstage.jst.go.jp/article/jmi/64/3.4/64_205/_article

Publication of results

Published

URL related to results and publications

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527850/

Number of participants that the trial has enrolled

20

Results

No DLT was found. There was no death event within 6 months after enrollment. However, one patient died due to disease progression.

No grade 4 adverse event or unexpected adverse reactions were found.

The response based on RECIST was 2 in CR, 13 in SD, 3 in PD, and 2 in NE. RR was 10%.

The scintigraphic response in the first course was 2 in CR, 5 in PR, 8 in SD, 4 in PD, and one in non-CR/non-PD. RR was 35%.

There was no death within 6 months of enrollment and OS and PFS were 100% and 80%, respectively.

Results date posted

2020

Year

02

Month

13

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2019

Year

05

Month

20

Day

Baseline Characteristics

Sex (F:M) 6:14
Age 51.2 +- 14.4 (range: 21-76) years

Severe local invasion at initial diagnosis (25%, 5/20)
Metastasis at initial diagnosis (25%, 5/20)
Local recurrence after surgical resection (20%, 4/20)
Metastasis after surgical resection (65%, 13/20)

Participant flow

We enrolled 20 patients between February 2016 and July 2017.

Adverse events

Adverse reactions by PT
Thrombocytopenia 15/20, 75.0%
Loss of appetite 14/20, 70.0%
Lymphopenia 13/20, 65.0%
Nausea 10/20, 50.0%
Leukopenia 10/20, 50.0%

Outcome measures

The best overall response rate based on RECIST was 10% (2/20) in complete response (CR), 65% (13/20) in stable disease (SD), 15% (3/20) in progressive disease (PD), and 10% (2/20) in not evaluated (NE). The response rate [partial response (PR) + CR] was 10%.
The scintigraphic response in the first course was 10%(2/20) in CR, 25% (5/20) in PR, 40% in SD (8/20), 20% in PD (4/20), and 5% in non-CR/non-PD (1/20). Response rate (PR + CR) was 35% (95% CI: 15.4-59.2%).
There was no death within 6 months of enrollment and overall survival (OS) rate was 100%. Four patients had progression events during the 6 months since enrollment and progression-free survival (PFS) at 6 months was 80.0%.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Main results already published

Date of protocol fixation

2015

Year

07

Month

30

Day

Date of IRB

2015

Year

10

Month

01

Day

Anticipated trial start date

2016

Year

02

Month

01

Day

Last follow-up date

2017

Year

07

Month

31

Day

Date of closure to data entry

2017

Year

11

Month

30

Day

Date trial data considered complete

2018

Year

01

Month

31

Day

Date analysis concluded

2018

Year

02

Month

28

Day

Other related information

Registered date

2015

Year

07

Month

30

Day

Last modified on

2020

Year

02

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021402