An Investigator-initiated Clinical Trial, First in Human study, wi th a natural-type micro RNA MIRX002, for patients with malignant pleural mesothelioma (MIRX002-01 repeated dose study)

JRCT ID: jRCT2061220015

Registered date:11/05/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Malignant pleural mesothelioma
• Date of first enrollment: 25/04/2022
• Target sample size: 18
• Study type: Interventional
• Intervention(s): Low (6mg/Body), medium (18mg/Body), and high (54mg/Body),doses of MIRX002 (miR-3140-3p and A6K mixture) given 3 times every 28 days (Day0, Day28 and Day56)

Outcome(s)

• Primary Outcome: Evaluation of safety and tolerability of repeated doses of the investigational drug (main item evaluation period: from the last dose within the third dose to 28 days).

Secondary Outcome

(1) Frequency of adverse events during the entire administration period (including the additional administration period)
(2) Evaluation of tumor shrinkage based on Modified RECIST
(3) Pharmacokinetics analysis of miR-3140-3p in blood

Key inclusion & exclusion criteria

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

Include criteria

(1) Patients who participated in the MIRX002-01 study and were judged by the investigator to have no safety problems with MIRX002 and to be expected to have therapeutic effects (Note 1).
(2) Patients with a definite diagnosis of malignant pleural mesothelioma by pleural biopsy, for which standard treatment is in effective or for which there is no appropriate treatment (clinical stage does not matter) (Note 2). The presence or absence of measurable lesions at the time of registration does not matter.
(3) Patients for whom the patient's written consent has been obtained for participation in this clinical trial.
(4) Age 20 years or older (regardless of gender).
(5) Patients with PS (ECOG) of 0 to 1
(6) Patients who are expected to survive for 12 weeks or more at the time of registration
(7) Patients who are judged by the investigator or investigator to consider the level of adhesions in the thoracic cavity and that there are still administrable sites in the thoracic cavity. However, it is essential that pleural effusion can be confirmed by chest CT examination.
(8) Blood test criteria (Within 14 days before registration)
1) White blood cell count is equal or over 3,000 / mm3 or neutrophil count is equal or over 2,000 / mm3
2) Hemoglobin is equal or over 9.0 g / dl
3) Platelet count is equal or over 10 x 104 / mm3
4) Total bilirubin is equal or less than 1.5 times the upper limit of the laboratory standard
5) AST equal or less than 2.5 times the standard upper limit of the inspection agency
6) ALT equal or less than 2.5 times the standard upper limit of the inspection agency
7) eGFR is equal or over 50 ml / min / 1.73 m2
8) Sp02 is equal or over 92% (or Pa02 is equal or over 60 mmHg) under atmospheric inhalation
(9) pregnant women must have a negative pregnancy test within 30 days prior to registration. Patients of childbearing age are those who have agreed to use appropriate contraceptive methods (Note 3) during the study period.
1) Pregnant women must follow contraceptive instructions for 140 days after administration of the study drug.
2) Men who have sexual intercourse with a fertile woman must follow contraceptive instructions for 84 days after administration of the study drug. Also, male subjects must not donate sperm during this period.
3) Men with azoospermia do not require contraception. Contraception is not required for fertile women who do not have sexual intercourse with the opposite sex, but pregnancy tests will be performed as specified in the clinical trial protocol.
a) Patients with platinum allergies
b) Patients suspected of having active autoimmune disease who are judged to be inappropriate for administration of ipilimumab or nivolumab
c) Other than a) and b), patients whose cancer board is medically judged to be unsuitable for existing treatment.
In this case, the evaluation results on the cancer board and the circumstances and reasons why the existing treatment cannot be started are recorded in the medical record and the case report.

Note 1: A situation in which no safety problem is observed means that a drug reaction equivalent to DLT (adverse event having a causal relationship of Grade 3 or higher (Grade 4 in hematological examination)) specified in the MIRX002-01 study continues at the time of registration. Indicates a situation that has not occurred.Expected efficacy indicates that the diagnostic imaging on the 28th day after administration specified in the MIRX002-01 study showed no clear progression of the disease.

Note 2: The investigator evaluates the eligibility criteria for the case only when the cancer board, which includes members other than the investigator, is judged to be a "case in which the existing treatment cannot be properly performed" from an objective standpoint. Can be incorporated into clinical trials. (If it has already been deliberated in the MIRX002-01 study, no action is required.) In principle, patients who refuse surgery will be treated after the existing treatment (combination therapy including platinum, ipilimumab, nivolumab).
After evaluation on the cancer board, it was judged that the existing treatment was not appropriate, including patients who refused surgery, and the patients experienced "(1) existing treatment", "(2) positioning of this clinical trial" and "(3) serious adverse events in this clinical trial." In some cases, the existing treatment may not be started. "After providing information in the consent explanation document, it will be possible to enroll in this clinical trial if the patient so desires. The cancer board uses the following criteria to determine that the existing treatment is not appropriate.
1) Patients with platinum allergies
2) Patients suspected of having active autoimmune disease who are judged to be inappropriate for administration of ipilimumab or nivolumab
3) Other than 1) and 2), patients whose cancer board is medically judged to be unsuitable for existing treatment.
In this case, the evaluation results on the cancer board and the circumstances and reasons why the existing treatment cannot be started are recorded in the medical record and the case report.

Note 3: Contraceptive methods such as condoms, pessaries, oral contraceptives, and intrauterine devices should be used under the guidance of the investigator.

Exclude criteria

(1) Patients who received other investigational drug within 4 weeks before the start of administration of the investigational medical product.
(2) Patients who received chemotherapy within 4 weeks before the start of administration of investigational medical product.
(3) Patients who received chest radiation therapy or immunotherapy within 12 weeks before the start of administration of investigational medical product.
(4) Patients who underwent surgery within 24 weeks before the start of administration of investigational medical product.
(5) Patients who have difficulty in intrathoracic administrationof the investigational medical product.
(6) Patients who are allergic to local anesthesia.
(7) Patients with serious heart disease.
(8) Patients with severe or difficult-to-control systemic diseases such as diabetes and hypertension.
(9) Patients with active infections (when systemic administration of antibacterial agents, antifungal agents, antiviral agents is required).
(10) Patients receiving systemic administration of immunosuppressants.
(11) Patients with active duplicate cancer (simultaneous dupllcate cancer/ cancer and metachronous duplicate cancer/ multiple cancer with a disease-free period of 2 years or less).
(12) Patients with brain metastases who are symptomatic or require treatment.
(13) Patients with a clear history of pulmonary fibrosis or interstitial pneumonia on chest CT and chest X-ray, all of which have a history of quality.
(14) Patients with pericardial fluid in need of treatment on CT imaging.
(15) Patients who have a plan to receive anticancer drug treatment while undergoing clinical trial schedule.
(16) Patients who have undergone organ transplantation in the past.
(17) Patients who have difficulty in participating in clinical trials due to psychosis or psychiatric symptoms.
(18) Pregnant or medium, patients who may or are willing to become pregnant.
(19) In addition, patients who are judged to be ineligible for this clinical trial by the investigator/ study division.

Related Information

• Primary Sponsor: Morihito Okada
• Source(s) of Monetary Support: Japan Agent for Medical Research and Development