Investigator-initiated phase 1 trial of antisense oligonucleotide against TUG1 for recurrent glioblastoma

JRCT ID: jRCT2041230136

Registered date:19/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: recurrent glioblastoma
• Date of first enrollment: 06/02/2024
• Target sample size: 24
• Study type: Interventional

Intervention(s)

Dosing frequency: 1 time /week
Dose Levels
Level 1: 0.1 mg/kg as TUG1 API
Level 2: 0.3 mg/kg as TUG1 API
Level 3: 0.6 mg/kg as TUG1 API
Level 4: 1.0 mg/kg as TUG1 API

Outcome(s)

• Primary Outcome: Safety

Secondary Outcome

Response rate based on HGG-RANO criteria
Progression-free survival
Pharmacokinetics
Overall survival
Duration of response

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

(1) Patients with a histological diagnosis of glioblastoma on a permanent specimen of surgical removal or biopsy specimen.
(2) Patients who are refractory or intolerant to standard treatment or for whom there is no treatment equivalent to standard treatment.
(3) Patients who have received concurrent postoperative TMZ chemoradiotherapy as initial treatment at the time of initial disease followed by at least 2 courses of maintenance TMZ therapy.
(4) Patients who have not undergone surgery after most recent recurrence or exacerbation: Patients who meet all of the following 1) to 4) on contrast-enhanced head MRI before enrollment; 1) If the patient is receiving steroids after recurrence or exacerbation, contrast-enhanced head MRI was performed 5 days after the start of steroid administration, 2) Recurrent or exacerbated glioblastoma is confirmed, 3) No acute or subacute cerebral hemorrhage, and 4) Has measurable lesions.
(5) Patients who have undergone surgery after most recent recurrence or exacerbation: Patients who meet all of the following 1) to 5); 1) Recurrence or exacerbation of glioblastoma is confirmed by contrast-enhanced head MRI before surgery at the time of recurrence or exacerbation, 2) Postoperative residual tumor size of recurrent tumor is confirmed by contrast-enhanced and non-contrast-enhanced head MRI within 3 days after surgery, 3) Anaplastic astrocytoma or glioblastoma is histologically confirmed in a permanent specimen at the time of reoperation, 4) Meet all of the following a) to c) on contrast-enhanced head MRI after 4 days postoperatively and before enrollment; a) If the patient is receiving steroids after recurrence or exacerbation, contrast-enhanced head MRI is performed after 5 days of the start of steroid administration, b) Either with or without measurable lesions, and c) Pre-enrollment head MRI shows no worsening of cerebral hemorrhage compared to head MRI performed within 3 days after surgery, and 5) if reoperated, patients from 21 to 28 days after reoperation.
(6) Patients who are more than 90 days from the date of last radiation exposure at the time of enrollment.
(7) Patients must be at least 18 years old and less than 75 years old on the date of enrollment.
(8) Patients whose latest KPS within 14 days prior to enrollment is 60 or more.
(9) Patients whose latest clinical laboratory test results within 14 days prior to enrollment meet the criteria.
(10) Patients who have given their written consent to participate in the study.

Exclude criteria

(1) Patients with extracerebral metastases.
(2) Patients with symptoms of significant intracranial hypertension.
(3) Patients with tumors in the cerebellum, brainstem, pituitary gland, optic nerve, or olfactory nerve at the time of initial onset or recurrence or exacerbation.
(4) Patients with intrathecal dissemination or cerebral gliomatosis.
(5) Patients with active multiple cancers.
(6) Patients with a history of chemotherapy, molecular targeted drugs, or radiotherapy in the head and neck region for other cancer
(7) Patients with infections requiring systemic administration of antimicrobial agents, antivirals, etc.
(8) Patients with positive HIV antibodies.
(9) Patients with positive HBs antigen or HCV antibody.
(10) Male patients whose QTcF exceed 450 msec or female patients whose QTcF exceed 470 msec on 12-lead ECG tests.
(11) Patients with severe cardiac disease.
(12) Patients with psychiatric disorders or psychiatric symptoms that make continued participation in the study difficult.
(13) Patients who have received prior anticancer therapy for glioblastoma within the period prior to the start of treatment with the study drug.
(14) Patients whose dose of steroids was increased within 2 weeks prior to the start of treatment with the study drug.
(15) Patients who received an investigational drug in another clinical trial within 4 weeks prior to the start of treatment with the study drug.
(16) Patients who cannot use Gadolinium-based head contrast agent.
(17) Pregnant, possibly pregnant, or lactating female patients.
(18) Patients who cannot agree to complete abstinence or effective contraception for at least 90 days after the last dose of the study drug.

Related Information

• Primary Sponsor: Saito Ryuta
• Secondary Sponsor: Kondo Yutaka
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,NANO MRNA Co., Ltd