An Investigator-initiated Clinical Trial, First in Human study, with a natural-type micro RNA MIRX002, for patients with malignant pleural mesothelioma

JRCT ID: jRCT2061210058

Registered date:09/12/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Malignant pleural mesothelioma
• Date of first enrollment: 01/12/2021
• Target sample size: 18
• Study type: Interventional
• Intervention(s): Intervention for patients for whom standard treatment is ineffective or for which there is no appropriate treatment

Outcome(s)

Primary Outcome

Safety and tolerability based on the following dose-limiting toxicity (DLT) definitions for a single dose of investigational medical product (main observation period 28 days)
DLT definition:
Based on the evaluation of adverse events based on the "Common Terminology Criteria for Adverse Events v5.0 Japanese translation JCOG version", Grade 3 that developed 28 days after the initial administration (Day 0) or by the day when discontinuation was decided. Of the adverse events described above (Grade 4 in hematological examination), those for which the investigator has determined that a causal relationship with the investigational medical product cannot be ruled out are referred to as DLT. In addition, febrile neutropenia is not a hematological adverse event but a non-hematological adverse event, and the investigator judges suitability for DLT. In addition, anemia requiring red blood cell transfusion and thrombocytopenia requiring platelet transfusion are judged to be applicable to DLT as hematological adverse events.
However, when the following adverse events occur, it was decided that the Safety and Efficacy Evaluation Committee would deliberate and determine the DLT instead of determining it as the DLT based solely on the judgment of the investigator.
* Infusion reaction
* Anaphylaxis
* Clinically important autoimmune reaction

Secondary Outcome

* Frequency of adverse events other than DLT in a single dose of the investigational medical product
* Evaluation of tumor shrinkage based on Modified RECIST

Key inclusion & exclusion criteria

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

Include criteria

(1) Patients with a definite diagnosis of malignant pleural mesothelioma by pleural biopsy, for which standard treatment is ineffective or for which there is no appropriate treatment (clinical stage does not matter). The presence or absence of measurable lesions at the time of registration does not matter.
(2) Patients for whom the patient's written consent has been obtained for participation in this clinical trial.
(3) Age 20 years or older (regardless of gender).
(4) Patients with PS (ECOG) of 0 to 1
(5) Patients who are expected to survive for 12 weeks or more at the time of registration.
(6) 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.
(7) Blood test criteria
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) SpO2 is equal or over 92% (or PaO2 is equal or over 60 mmHg) under atmospheric inhalation
(8) When incorporating pregnant women, confirm eligibility according to the following criteria.
1) Pregnant women must have a negative pregnancy test within 30 days prior to registration.
2) Pregnant women must follow contraceptive instructions for 84 days after administration of the investigational medical product.
3) Men who have sexual intercourse with a fertile woman must follow the instructions for contraception for 84 days after administration of the study drug. Also, male subjects must not donate sperm during this period.
4) 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.

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