UMIN-CTR Clinical Trial

Public title

A clinical study of adenovirus mediated Reduced Expression in Immortalized Cells/Dickkopf-3 (REIC/Dkk-3) gene therapy for malignant pleural mesothelioma

Acronym

Malignant pleural mesothelioma gene therapy using REIC

Scientific Title

A clinical study of adenovirus mediated Reduced Expression in Immortalized Cells/Dickkopf-3 (REIC/Dkk-3) gene therapy for malignant pleural mesothelioma

Scientific Title:Acronym

Malignant pleural mesothelioma gene therapy using REIC

Region

Japan

Condition

malignant pleural mesothelioma

Classification by specialty

Chest surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

This is a Phase I, open-label, dose-escalation trial in patients with malignant pleural mesothelioma.
Primary Objective:
To assess the safety of in-situ therapy with the REIC/Dkk-3 gene in patients with malignant pleural mesothelioma.
Secondary Objective:
To study the in vivo pharmacology and effectiveness of the REIC/Dkk-3 gene therapy as measured by; (a) Morphologic and cytotoxic changes in the specimen of a pleural biopsy after treatment, and (b) to assess the local and systemic immune-stimulatory activity

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase I,II

Primary outcomes

Tolerability:
Performance Status
CBC (including platelets, fibrinogen, SGPT, lactic dehydrogenase)
Adverse events (AEs)
Physical examination (PE)
Vital signs (VS)
Clinical laboratory values

Key secondary outcomes

Evaluation of gene therapy
Chest CT (1, 2, 4 weeks)
lymphocyte analysis (2, 3, 4 weeks)

Study type

Interventional

Basic design

Parallel

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

4

Purpose of intervention

Treatment

Type of intervention

Medicine

Gene

Interventions/Control_1

1.0 x 10E11 virus particle

Interventions/Control_2

3.0 x 10E11 virus particle

Interventions/Control_3

1.0 x 10E12 virus particle

Interventions/Control_4

3.0 x 10E12 virus particle

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

75

years-old

>

Gender

Male and Female

Key inclusion criteria

1) Pathologically proven malignant pleural mesothelioma
2) Tumor lesions that can be detected by diagnostic imaging
3) Patients should be at least 20 years old and younger than 75 years old
4) ECOG performance status of 0 or 1
5) If radiotherapy was performed before case entry, irradiation should be within 25% of the bone with hematopoietic capacity, and 21 or more days should elapse at case entry since the final irradiation
6) If surgical therapy other than extrapleural pneumonectomy was performed, 21 or more days should elapse at case entry since the day of operation and there should be evaluable lesions
7) Functions of main organs are maintained, satisfying the following conditions
Hemoglobin concentration >= 9.0 g/dL
White blood cell count >= 3,000/mm3 or Neutrophil count >= 2,000/mm3
Platelet count >= 100,000/mm3
AST and ALT <= 2.5 X of normal values in each institution
Total bilirubin <= 1.5 X of normal values in each institution
Serum creatinine < 1.5 mg/dL
SpO2 >= 92% (room air)
ECG: within normal limit
8) Patients expected to be alive for at least 12 weeks since case entry
9) Written consent by patients themselves should be obtained.
10) For chemotherapy, the patients should be either of the following a, b or c.
a. Patients refractory to the chemotherapy including pemetrexed, and more than 3 weeks should elapse at case entry since the final administration.
b. Patients who can not undergo chemotherapy due to the severe hypersensitivity
c. Patients who refuse the systemic chemotherapy for malignant pleural mesothelioma
11) For radical surgery, the patients should be either of the following a or b.
a. Patients not indicated for extrapleural pneumonectomy
b. Patients who refuse the radical surgery for malignant pleural mesothelioma

Key exclusion criteria

1) Patients with poor-controlled systemic disease
2) Patients with active infections
3) Patients with active double cancer
4) Patients with brain metastasis
5) Patients with interstitial pneumonia or lung fibrosis detected by CXR
6) Patients with recurrent malignant pleural mesothelioma after extrapleural pneumonenctomy or Patients with pneumonectomy due to the disease other than malignant pleural mesothelioma
7) Patients with cardiac effusion requiring the treatment
8) Patients more than 1:1000 titer of neutralizing antibody for adenovirus
9) Patients injected with unapproved drugs within 4 weeks
10) Pregnant or breast-feeding females and females who have a possibility of pregnancy or lactation or patients who does not intend to use birth control
11) Patients who can not use contraception for 90 days after the final administration of REIC
12) Other patients judged to be ineligible by the investigator

Target sample size

24

Name of lead principal investigator

1st name
Middle name
Last name	Shinichi Toyooka

Organization

Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences

Division name

Clinical Genomic Medicine

Zip code

Address

2-5-1 Shikata-cho, Kita-ku, Okayama

TEL

086-235-7436

Email

toyooka@md.okayama-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Hiromasa Yamamoto, Yuho Maki

Organization

Okayama University Hospital

Division name

Thoracic Surgery

Zip code

Address

2-5-1 Shikata-cho, Kita-ku, Okayama

TEL

086-235-7436

Homepage URL

http://www.nigeka-okayama-u.jp/chest/medical_016.html

Email

cgm@okayama-u.ac.jp

Institute

Okayama University Hospital

Institute

Department

Personal name

Organization

Okayama University hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan

Co-sponsor

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

岡山大学病院（岡山県）
Okayama University Hospital（Okayama）

Date of disclosure of the study information

2014

Year

04

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

Terminated

Date of protocol fixation

2014

Year

02

Month

19

Day

Date of IRB

Anticipated trial start date

2014

Year

05

Month

01

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2014

Year

03

Month

30

Day

Last modified on

2019

Year

05

Month

03

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015773