UMIN-CTR Clinical Trial

Public title

A Phase I study of intratumoral administration of TDM-812 in patients with treatment-resistant breast cancer (RPN2siRNA)

Acronym

A Phase I study of intratumoral administration of TDM-812 in patients with treatment-resistant breast cancer(RPN2siRNA)

Scientific Title

A Phase I study of intratumoral administration of TDM-812 in patients with treatment-resistant breast cancer (RPN2siRNA)

Scientific Title:Acronym

A Phase I study of intratumoral administration of TDM-812 in patients with treatment-resistant breast cancer(RPN2siRNA)

Region

Japan

Condition

treatment-resistant breast cancer

Classification by specialty

Hematology and clinical oncology

Breast surgery

Classification by malignancy

Malignancy

Genomic information

NO

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

Primary outcomes

safety and tolerability

Key secondary outcomes

ratio of adverse events, local response rate (RECIST1.1)

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

Name of lead principal investigator

1st name
Middle name
Last name	Kenji Tamura

Organization

National Cancer Center Hospital

Division name

breast cancer and medical oncology

Zip code

Address

5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

TEL

03-3542-2511-7390

Email

ketamura@ncc.go.jp

Name of contact person

1st name
Middle name
Last name	Ritsuko Nagasaka

Organization

National Cancer Center Center for Research Administraion and Support

Division name

Research Management Section

Zip code

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

Institute

National Cancer Center

Institute

Department

Personal name

Organization

Ministry of Health, Labour and Welfare

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

3D Matrix Co, Ltd.

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

国立がん研究センター中央病院

Date of disclosure of the study information

2015

Year

03

Month

13

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

2015

Year

02

Month

19

Day

Date of IRB

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

Other related information

Registered date

2015

Year

03

Month

13

Day

Last modified on

2018

Year

03

Month

30

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019489