UMIN-CTR Clinical Trial

Public title

Phase 1 clinical trial of an intrathoracic administration of adenoviruses harboring the NK4 gene (AdCMV-NK4) for subjects with unresectable malignant pleural mesothelioma

Acronym

Gene therapy with NK4-expressing adenoviruses for malignant pleural mesothelioma

Scientific Title

Phase 1 clinical trial of an intrathoracic administration of adenoviruses harboring the NK4 gene (AdCMV-NK4) for subjects with unresectable malignant pleural mesothelioma

Scientific Title:Acronym

Gene therapy with NK4-expressing adenoviruses for malignant pleural mesothelioma

Region

Japan

Condition

malignant pleural mesothelioma

Classification by specialty

Medicine in general	Pneumology	Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To confirm the safety of intrathoracic administration of AdCMV-NK4 and determination of the maximum tolerance dose for the effective dose

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase I

Primary outcomes

Evaluation of frequency of the adverse events and limiting toxicity (DLT)

Key secondary outcomes

antitumor effect (response to the treatment)

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Gene

Interventions/Control_1

Three graded AdCMV NK4 doses, low dose group (1000000000vp), medium dose group (10000000000vp) and high dose group (100000000000vp), are examined as a dose-escalation study. One dose of AdCMV NK4 will be injected into the thoracic cavity of a patient on day1 of the study. A patient is monitored for 28 days after the injection and the dose limiting toxicity, antitumor effects and biological responses are examined.
The study will started at a low dose group (n=3) and move on to a medium (n=3) and a high dose group (n=3) unless major adverse effects are produced. Admission to the hospital will be required until no viral excretion was confirmed in each samples (sputum, saliva, urine, and serum) by PCR.

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

80

years-old

>=

Gender

Male and Female

Key inclusion criteria

Patients pathologically diagnosed as malignant pleural mesothelioma
Unresectable cases, including recurrence after surgery, or those who reject surgery
Recurrent cases or refractory cases to chemotherapies
(At least four weeks intervals are required from the last course of chemotherapy)
Patients who reject chemotherapies
Patients who have not underwent thoracic radiotherapy previously
Patients with written informed consent, those fully explained about the study using a document
ECOG Performance status 0 to 1
Patients with not being pregnant nor lactating. Patients who agree to contraception during the study period, and/or those agree to inform their doctors whenever they or their spouse get pregnant
Patients with life expectancy longer than 3 months
Patients who have an enough space in thoracic cavity for viral injection
Patients who are considered safe to participate to the study, approved by the principle investigator or the collaborators
Patients with enough organic functions and laboratory findings as follows
White Blood Cell >= 3000/mm3, or Neutrophils >=2000/mm3
Platelet >=10x104/mm3
Hemoglobin <=9.0/dl
Total Bilirubin <= x 1.5 of upper-limit of normal range
ALT(GOT)/AST(GPT) <= x 2 of upper-limit of normal range
Alkaline phosphatase <=x5 of upper-limit of normal range
Creatinine <1.5mg/dl
PT and APTT: within normal range
SPO2 at breathing room air >=92%
Electric cardiogram: within normal range

Key exclusion criteria

Patients with active or uncontrolled infectious diseases and /or the severe complications
Patients who have another malignancy besides malignant mesothelioma, synchronous or metachronous. Patients who have achieved complete cure or have progression free interval longer than 2 years are acceptable
Patients who have symptomatic brain metastatic foci and / or require a treatment for it
Patients who do not have enough intra-thoracic room for viral injection
Patients who have participated in other clinical trial with approved or unapproved medicine within 4 weeks before the entry in this study
Patients who are scheduled to receive another anticancer drug during the study period
Patients who have already treated with pleurodesis for mesothelioma
Patients who have peripheral nerve palsy more than grade 2 in CTCAE vers 4.0 at the entry
Patients who have apparent interstitial diseases and pulmonary fibrosis on chest X ray
Patients who have any problems including mental, familial, social or geographic issues that prevent good compliance to achieve this study
Patients who have already undergone a treatment using adenoviral vectors
Patients who have a treatment history of auto or allograft organ transplantation
Patients who are positive for HIV antigen, HBV antigen, HCV antibody, and HTLV 1 antibody
Patients who are judged as inappropriate to participate this study by the principal investigator and the collaborators

Target sample size

9

Name of lead principal investigator

1st name
Middle name
Last name	Koichiro Tatsumi

Organization

Graduate School of Medicine, Chiba University

Division name

Department of Respirology

Zip code

Address

1-8-1 inohana chuo-ku Chiba Japan

TEL

81-43-222-7171

Email

tatsumi@faculty.chiba-u.jp

Name of contact person

1st name
Middle name
Last name	Yuji Tada

Organization

Graduate School of Medicine, Chiba University

Division name

Department of Respirology

Zip code

Address

1-8-1 inohana chuo-ku Chiba Japan

TEL

81-43-222-7171

Homepage URL

http://www.m.chiba-u.ac.jp/class/respir/index.html

Email

ytada@faculty.chiba-u.jp

Institute

Graduate School of Medicine, Chiba University

Institute

Department

Personal name

Organization

NICHIAS corporation

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Chiba cancer center
Tokyo women's univesity Yachiyo medical center
Toho university omori medical center

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

千葉大学医学部附属病院　
Chiba university hospital

Date of disclosure of the study information

2015

Year

01

Month

01

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

08

Month

22

Day

Date of IRB

Anticipated trial start date

2015

Year

01

Month

06

Day

Last follow-up date

2018

Year

12

Month

31

Day

Date of closure to data entry

2018

Year

12

Month

31

Day

Date trial data considered complete

2018

Year

12

Month

31

Day

Date analysis concluded

2019

Year

03

Month

31

Day

Other related information

Registered date

2014

Year

11

Month

28

Day

Last modified on

2019

Year

01

Month

31

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018351