A phase I clinical trial of intratumoral administration of natural microRNA to replenish recurrent lesions in cervical lymph nodes of patients with head and neck cancer.

JRCT ID: jRCT2031240644

Registered date:29/01/2025

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: HNSCC with recurrent cervical lymph node
• Date of first enrollment: 14/02/2025
• Target sample size: 7
• Study type: Interventional
• Intervention(s): Sigle arm, dose ascending study. The study intervention (intratumoral administration of MIRX002) will be administered once every 14 days to all cervical lymph node lesions that recur, with end-of-study evaluation and examination to be performed 14 days (Day 28) after the second intratumoral administration. Thereafter, salvage surgery (surgical resection of recurrent lymph node lesions) will be performed and pathological evaluation of the resected tissue will be performed. Patients will be followed up to 2 weeks (Day 42) for safety confirmation after salvage surgery. MIRX002 consists of the active ingredient miR-3140-3p and the additive A6K, and is prepared just before use and administered into the tumor in a prespecified amount. Intratumor administration should be performed under anesthesia, and the volume of MIRX002 administered per dose should be 0.2 mL per cm3 of tumor volume. The total volume of lymph node lesions for intratumor administration should be limited to 450 cm3 or less. The dosages for each group are, 0.1 mg/mL as miR-3140-3p conc. at Level 1, 0.3 mg/mL at Level 2, and 0.5 mg/mL at Level 3.

Outcome(s)

Primary Outcome

1. Incidence of DLT as defined in the study protocol
2. Adverse events based on the National Cancer Institute's Common Terminology Criteria for Adverse Events v5.0
3. General condition (body weight, ECOG-PS)
vital signs
4. Laboratory test results (hematology, blood biochemistry, coagulation tests, urinalysis, 12-lead EKG)

Secondary Outcome

1. Objective tumor shrinkage effect based on RECIST v1.1
2. Pathologic Response Effect in Lymph Node Lesions
3. Completion rate of salvage surgery

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable

Include criteria

All of the following criteria must be met in order to participate in this study
(1) Patients with cytology or histology confirmed head and neck cancer with primary site in the oral cavity, hypopharynx, mid-pharynx, or larynx
(2) Patients with recurrence in cervical lymph nodes after radical resection of the primary lesion
(3) Patients with resectable cervical lymph node lesions (Total volume of recurrent cervical lymph node lesions by CT or MRI scan prior to study intervention must be less than 450 cm 3) of at least 15 mm in short diameter
(4) Patients with no recurrent lesions other than cervical lymph nodes on CT, MRI or PET scan prior to study intervention
(5) Patients who have given written informed consent to participate in this study and have given their free written consent
(6) Patients (of any gender) ages 18 years and older
(7) Patients with ECOG Performance Status of 0 or 1
(8) Patients with adequate bone marrow, kidney, and liver function:
1. White blood cell (WBC) >= 3,000/ micro L
2. Absolute neutrophil count (ANC) >= 1,500/ micro L
3. Platelet count >= 100,000/ micro L
4. Hemoglobin >= 9.0 g/dL
5. Creatinine within normal range
6. AST <= 3.0 x ULN
7. ALT <= 3.0 x ULN
8. Alkaline phosphatase (ALP) <= 2.5 x ULN
9. Total bilirubin <=1.5 x ULN
(9) All female patients of childbearing potential must have a negative serum pregnancy test prior to the start of the study intervention. Patients of childbearing potential must agree to use effective contraception during the study intervention

Exclude criteria

Persons who meet any of the following criteria are not eligible for this study
(1) Patients who received other study interventions within 4 weeks prior to the start of the study intervention
(2) Patients who received chemotherapy within 4 weeks prior to study intervention
(3) Patients who received radiation therapy within 4 weeks prior to the start of the study intervention
(4) Patients who received immune checkpoint inhibitors within 12 weeks prior to study intervention
(5) Patients expected to have difficulty with intra-tumor administration of MIRX002
(6) Patients with a history of allergy to general or local anesthesia
(7) Patients with serious heart disease
(8) Patients with severe or difficult-to-control systemic diseases (e.g., diabetes mellitus, hypertension, etc.) as judged by the investigator, etc.
(9) Patients with active infections (requiring systemic administration of antibiotics, antifungals, antivirals, etc.)
(10)Patients receiving systemic administration of steroids or immunosuppressive agents
(11)Patients with active overlapping cancers (simultaneous overlapping cancers or iatrogenic overlapping cancers with a disease-free interval of 2 years or less)
(12)Patients with brain metastases that are symptomatic or require treatment
(13)Patients with pericardial effusions requiring treatment
(14)Patients scheduled to receive other anticancer therapy during the study period
(15)Patients who have received organ transplants in the past
(16)Patients with psychosis or psychotic symptoms who are unable to participate in the study
(17)Pregnant patients, lactating patients (incorporation due to interruption of lactation is also not allowed), patients who may be pregnant or intend to become pregnant
(18)Patients deemed ineligible for the study by the investigator or others for any other reason

Related Information

• Primary Sponsor: Tahara Makoto
• Secondary Sponsor: Takahashi Kazuhiro