UMIN-CTR Clinical Trial

Basic information
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
Condition	malignant pleural mesothelioma
Classification by specialty	Chest surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
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

Assessment
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)

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
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

Eligibility
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

Research contact person
Last 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

Public contact
1st 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

Sponsor
Institute	Okayama University Hospital
Institute
Department

Funding Source
Organization	Okayama University hospital
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

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

Other administrative information
Date of disclosure of the study information	2014 Year 04 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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

Progress
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
Other related information

Management information
Registered date	2014 Year 03 Month 30 Day
Last modified on	2019 Year 05 Month 03 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000015773