UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Phase 1 clinical trial of an intrathoracic administration of adenoviruses harboring the NK4 gene (AdCMV-NK4) for subjects with unresectable malignant pleural mesothelioma
Title of the study (Brief title)	Gene therapy with NK4-expressing adenoviruses for malignant pleural mesothelioma
Region	Japan

Condition
Condition	malignant pleural mesothelioma
Classification by specialty	Medicine in general Pneumology Hematology and clinical oncology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
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

Assessment
Primary outcomes	Evaluation of frequency of the adverse events and limiting toxicity (DLT)
Key secondary outcomes	antitumor effect (response to the treatment)

Base
Study type	Interventional

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

Intervention
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

Eligibility
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

Research contact person
Name of lead principal investigator	Koichiro Tatsumi
Organization	Graduate School of Medicine, Chiba University
Division name	Department of Respirology
Address	1-8-1 inohana chuo-ku Chiba Japan
TEL	81-43-222-7171
Email	tatsumi@faculty.chiba-u.jp

Public contact
Name of contact person	Yuji Tada
Organization	Graduate School of Medicine, Chiba University
Division name	Department of Respirology
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

Sponsor
Institute	Graduate School of Medicine, Chiba University
Institute
Department

Funding Source
Organization	NICHIAS corporation
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor	Chiba cancer center Tokyo women's univesity Yachiyo medical center Toho university omori medical center
Name of secondary funｄer(s)

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

Other administrative information
Date of disclosure of the study information	2015 Year 01 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 08 Month 22 Day
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

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2014 Year 11 Month 28 Day
Last modified on	2019 Year 01 Month 31 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018351