UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	A Phase I study of intratumoral administration of TDM-812 in patients with treatment-resistant breast cancer (RPN2siRNA)
Title of the study (Brief title)	A Phase I study of intratumoral administration of TDM-812 in patients with treatment-resistant breast cancer(RPN2siRNA)
Region	Japan

Condition
Condition	treatment-resistant breast cancer
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	1) To evaluate safety and torelability of intratumoral administration of TDM-812 (RPN2siRNA/A6K complex) 2) To determine the recommended dose of TDM-812 in intratumoral administration for future clinical use
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase I

Assessment
Primary outcomes	safety and tolerability
Key secondary outcomes	ratio of adverse events, local response rate (RECIST1.1)

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	TDM-812 is intratumorally administered weekly at each dose level.
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	Not applicable
Gender	Female
Key inclusion criteria	[Disease characteristics] 1. Inoperable or relapse breast cancer 2. Histological confirmation of invasive breast cancer(e.g., invasive ductal carcinoma, and special types) 3. A treatment history of anthracycline (e.g., doxorubicin and epirubicin) and taxane (e.g., paclitaxel, docetaxel, and nab-paclitaxel) agents, irrespective of the type of combination or treatment order. [Patient characteristics] 1. Provision of signed informed consent. 2. Patients aged >=20 years women. 3. Eastern Cooperative Oncology Group Performance Status (PS) of 0 to 2. 4. Having at least one palpable lesion with which to evaluate objective response, based on the New RECIST guideline ver.1.1 5. Having lesions applicable to 4) which to be able to inject investigational drug 6. Having lesions applicable to 4) which to be able to conduct repeated biopsy 7. Patients with the following values in their latest laboratory tests, conducted within 7 days prior to the enrollment -Neutrophil count >=1,000/mm3 -Platelet count >=75,000/mm3 -Total bilirubin <=1.5 mg/dL*ULN -Serum ALT and AST <=100 U/dL (<=150 U/dL for patients with hepatic metastasis) -Serum creatinine <=1.2 mg/dL -ECG Normal or minimal changes not requiring treatment (ECG measurement may be performed within 28 days prior to the enrollment). 8. Recovery to grade <=1 from all toxicities related to chemotherapy and radiotherapy, except for stable grade <=2 sensory neuropathy and alopecia. 9. In case of fertile woman, Patients fulfilled the following condition a)not performed sex within 30 days before enrollment b)provision of consent to conduct effective contraception from study enrollment to 6 months after study discontinuation.
Key exclusion criteria	1. Patients who meet the following conditions. a)Patients who received other investigational drug(s) within 4 weeks before enrollment b)Patients who received systemic therapy within 3 weeks before enrollment c)Patients who received surgery within 4 weeks before enrollment d)Patients who received radiation in wide area within 4 weeks before enrollment or received palliative radiation within 2 weeks before enrollment e)Patients who have received radiation to planned lesion of administration of investigational drug 2. Patients with brain metastasis, except for patients who have completed topical therapy and stopped treatment with glucocorticoid agents at least 4 weeks before enrollment. For these patients, stable disease must be confirmed by symptoms and the images at the time of enrollment compared to the one obtained at least 4 weeks before enrollment.. 3. Patients with systemic active infection. 4. Patients with active infection at planned lesions of administration of investigational drug. 5. Patients with allergy to local anesthetic 6. Patients with respiratory failure requiring oxygen inhalation therapy 7. Patients requiring anti-coagulant therapy 8. Patients with serious cardiovascular disease (congestive cardiac failure within 6 months before enrollment, history of unstable angina or myocardial infarction, or serious arrhythmia) 9. Patients with difficulty following the study procedures due to psychiatric disease or psychological symptoms 10. Patients who meet the following conditions. a)HBs-Ag positive (In case HBs-Ag is negative but HBs-Ab and/or HBc-Ab are/is positive, only HBV-DNA negative can be allowed to enroll.) b)HCV-Ab positive and/or HCV-RNA positive c)HIV-Ab positive 11. Pregnant or breast-feeding women, or women of child bearing potential who intend to become pregnant 12. Patients who should not participate in the study, as judged by the investigator(s)
Target sample size	30

Research contact person
Name of lead principal investigator	Kenji Tamura
Organization	National Cancer Center Hospital
Division name	breast cancer and medical oncology
Address	5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
TEL	03-3542-2511-7390
Email	ketamura@ncc.go.jp

Public contact
Name of contact person	Ritsuko Nagasaka
Organization	National Cancer Center Center for Research Administraion and Support
Division name	Research Management Section
Address	5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
TEL	03-3542-2511-5661
Homepage URL
Email	RPN2-office@ml.res.ncc.go.jp

Sponsor
Institute	National Cancer Center
Institute
Department

Funding Source
Organization	Ministry of Health, Labour and Welfare
Organization
Division
Category of Funding Organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)	3D Matrix Co, Ltd.

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	国立がん研究センター中央病院

Other administrative information
Date of disclosure of the study information	2015 Year 03 Month 13 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 02 Month 19 Day
Anticipated trial start date	2015 Year 03 Month 18 Day
Last follow-up date	2017 Year 07 Month 31 Day
Date of closure to data entry	2017 Year 07 Month 31 Day
Date trial data considered complete	2017 Year 09 Month 30 Day
Date analysis concluded	2017 Year 11 Month 30 Day

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

Management information
Registered date	2015 Year 03 Month 13 Day
Last modified on	2018 Year 03 Month 30 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019489