Phase I study to evaluate the safety of TDM-812 intra-tumor administration targeted for refractory breast cancer

JRCT ID: jRCT2031200057

Registered date:22/06/2020

Basic Information

• Recruitment status: Suspended
• Health condition(s) or Problem(s) studied: Breast cancer
• Date of first enrollment: 22/06/2020
• Target sample size: 18
• Study type: Interventional

Intervention(s)

For the target tumor, the dose settled at each dose level would be administered in tumor, subsequently being administered every 1 week. Each dose level is as follows:
Level 1: RPN2siRNA 1.0mg, 2.0mL of 0.5% AGK/glucose
Level 2: RPN2siRNA 2.0mg, 4.0mL of 0.5% AGK/glucose
Level 3: RPN2siRNA 3.0mg, 6.0mL of 0.5% AGK/glucose

Outcome(s)

• Primary Outcome: Safety, tolerability
• Secondary Outcome: Onset rate of Adverse Events, Success ratio for local lesion

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

<Disease Characteristics>
1)Patients with inoperable or recurrent breast cancer
2)Patients diagnosed as invasive breast cancer (infiltrating ductal carcinoma or specific type)
3)Patients with previous treatment history of anthracycline and taxane-based agents (No regulations of the drug type and/or
total dose)
-In case of unresectable and/or metastatic breast cancer,
treatment history of 3 or more regimens including anthracycline and taxane-based agents is required.
-In case of recurrent breast cancer with treatment history of
anthracycline-based agent only as a perioperative adjuvant
chemotherapy, treatment history of 2 or more regimens including taxane-based agent after recurrence is required.
-In case of recurrent breast cancer with treatment history of
Anthracycline and taxane-based agents as a perioperative adjuvant chemotherapy, treatment history of 1 or more regimens after recurrence is required.
-For the treatment history of chemotherapy, the difference of regimen with/without Trastuzumab is not considered.
Hormone therapy and single Trastuzumab agent is not regarded as 1 regimen.

<Patient Characteristics>
1)Patients from whom obtained the written informed consent for participating in this
clinical study.
2)Women of 20 years or older at the point of obtaining the informed consent.
3)Patients with 0~2 scores of Performance Status of Eastern Cooperative Oncology Group (ECOG) at the point of obtaininginformed consent.
4)Patients who have 1 or more palpable and measurable lesions* from the body surface at the point of pre-registration examination.
*In case of receiving radiotherapy, patients who have 4 weeks or more interval from the final day of radiotherapy to the start day of administering IP and have apparently aggravated lesions.
5)Patients who can be administered IP via intra-tumor route to the corresponding lesion site written in above 4).
6)Patients with the following organ functions (the clinical
examination value should be determined by the most recent value within 7 days
prior to registration. ECG should be determined by image within 28 days prior to registration.)
-Neutrophil count: 1,000/mm3 or more
-Platelet count: 75,000/mm3 or more
-Total bilirubin: 1.5mg/dL or less
-Serum AST/ALT: 100U/L or less
(For patients with hepatic metastasis, 150U/L or less)
-Serum creatinine: 1.2mg/dL or less
-ECG image: Normal or mild change that is not required to be cured.
7)Patients whose toxicity related to pre-treatment recovered to Grade 1 or less at the point of pre-registration examination. However, for patients with stable Grade 2, sensory neuropathy, alopecia and nail loss can be registered.
8)In case of women possible to be pregnant*, patients who did not have sexual intercourse without contraception within 30 days before registration, and consent to adopt highly effective contraceptive method** from the registration through 6 months after discontinuation of the clinical trial.
*:Women possible to be pregnant does not correspond to menopause regulated in term 7.2.4., and is defined not to receive the permanent contraceptive surgery such as total hysterectomy.
**:Complete examples for highly effective contraceptive methods are Intra-uterine device (IUD), double-barrier method (concomitant use of condom with spermicide and contraceptive pessary, etc.) , and oral contraceptives.

Exclude criteria

1)Patients correspond to either of the followings:
-Patients given other IPs within 4 weeks before the start day of IP administration.
-Patients received other chemotherapy and/or immunotherapy within 3 weeks before the start day of IP administration.
-Patients undergone surgical operation requisite for total anesthesia within 4 weeks before the start day of
IP administration.
-Patients received radiotherapy with wide-range irradiation within 4 weeks before the start day of IP administration, or patients received radiotherapy with local irradiation for relieving care within 2 weeks before the
start day of IP administration.
-Patients received radiotherapy to the targeting lesion of IP administration within 4 weeks before the start
day of IP administration.
2)Patients with brain metastasis. However, patients who completed the local treatment and discontinued the use of glucocorticoid at the point of the 4th week before registration are eligible for inclusion.
However, patient's condition caused by brain metastasis and image (imaging brain CT or imaging brain
MRI) need to be stable.
For stabilization of images, comparison of image more than 4 weeks before registration with one at the
latest point of registration is necessary for judgment.
3)Patients complicated with active and systemic infectious disease at the point of pre-registration
examination.
4)Patients complicated with active infectious disease in the targeting lesion of IP administration.
5)Patients with allergy to local anesthesia.
6)Patients with respiratory failure requisite for oxygen inhalation therapy at the point of pre-registration
examination.
7)Patients who require anti-coagulant therapy at the point of pre-registration examination. (However, the use of heparin to prevent blood coagulation in the line of administration is permitted.)
8)Patients with severe cardiovascular disease (congested heart failure within 6 months before registration,
unstable angina, history of myocardial infarction, or severe arrhythmia).
9)Patients difficult to participate in clinical trial due to mental illness or mental condition.
10)Patients with positive reaction of HBs antigen, HCV antibody
(If positive, HCV-RNA should be determined), and/or HIV antibody.
-If patients with negative for HBs turned out to be positive for HBs antibody or HBc antibody, HBV-DNA should be determined.
-Patients already cured infectious disease (negative for HBV-DNA or HCV-RNA) are eligible for inclusion.
Patients with positive for HBV-DNA or HCV-RNA are not eligible for inclusion.
11)Pregnant or lactating women. Women who may be pregnant or are willing to be pregnant (Women who interrupted lactation are regarded to be not eligible for inclusion).
12)Patients judged to be not eligible for this clinical trial by principal investigator or sub investigator.

Related Information

• Primary Sponsor: Kitano Atsuko
• Source(s) of Monetary Support: 3-D Matrix, Ltd.