Trial to Evaluate the Safety of TTAC-0001(Tanibirumab) in Recurrent Glioblastoma

Study Overview
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Brief Summary
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Study Design - Multicenter, open-label, 3 arms, stepwise, phase Ⅱa clinical trial Study objective: Primary - To evaluate the safety of TTAC-0001 in patients with recurrent glioblastoma. Secondary - To determine the efficacy of TTAC-0001 in patients with recurrent glioblastoma. Exploratory To evaluate pharmacokinetic (PK) parameters of TTAC-0001 in patients with recurrent glioblastoma To evaluate pharmacodynamic (PD) parameters by clinical biomarker test Study Methodology Patients will be sequentially enrolled from the 1st arm. An enrollment criterion to the next arm is defined as no patients in the previous treatment arm showing grade ≥3 of hemangioma or other Dose Limiting Toxicities (DLT). A safety review committee (SRC) will convene to determine the patient's safety with a decision on enrollment into the next arm or change in dosing frequency of study drug in the above case. A patient who is withdrawn from the study before the completion of the 1st cycle can be replaced with another patient. Patients will be treated for up to 1 year, unless a cause for termination occurs, such as progression of disease (PD) or the withdrawal of consent.

Official Title
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A Multicenter, 3-Arm, Open-Label, Phase Ⅱa Clinical Trial to Evaluate the Safety and Efficacy of TTAC-0001, a Fully Human Monoclonal Antibody in Patients With Recurrent Glioblastoma

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Drug: TTAC-0001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both male and female patients ≥19 years old Diagnosed with primary glioblastoma by histopathological examination and confirmed recurrent glioblastoma by magnetic resonance imaging (MRI) scans after concomitant temozolomide chemotherapy with radiotherapy (CCRT). One previous recurrence/progression of glioblastoma with reintroduction/altered schedule of temozolomide is allowable. At least one confirmed measurable lesion or non measurable lesion by response assessment in neuro-oncology (RANO) criteria Karnofsky Performance Status (KPS) ≥ 80 A person who satisfies the following criteria in hematologic, renal, and hepatic function tests At least 12 weeks of expected survival time Signed informed consent Exclusion Criteria: Diagnosed with other malignant tumor within 2years Uncontrolled HT or seizure, class III or IV heart failure, oxygen dependent disease, active psychiatric disorder Not recovered grade 2 AE due to previous CCRT Major surgery or other investigational drug treatment within 4 weeks Pregnant/lactating female and female/male potential childbearing without contraception Severe drug hypersensitivity or hypersensitivity to a therapy similar to the study drug Expectation of poor compliance Previous therapy with VEGF targeted agent

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients will be treated with 8mg/kg of TTAC-0001 on day 1, day 8 and day 15 in every 4 weeks of cycle. | Drug: TTAC-0001<br>* Calculated amount of drug will be diluted with normal saline and administered intravenously.<br>* Other names: Tanibirumab;|
| Experimental: Cohort 2<br>Patients will be treated with 12mg/kg of TTAC-0001 on day 1, day 8 and day 15 in every 4 weeks of cycle. | Drug: TTAC-0001<br>* Calculated amount of drug will be diluted with normal saline and administered intravenously.<br>* Other names: Tanibirumab;|
| Experimental: Cohort 3<br>Patients will be treated with 12mg/kg of TTAC-0001 weekly in every 4 weeks of cycle. | Drug: TTAC-0001<br>* Calculated amount of drug will be diluted with normal saline and administered intravenously.<br>* Other names: Tanibirumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS at 6-month time point |  | 6 months | 
| Objective response rate (ORR) | The rate of complete response and partial response assessed according to RANO criteria. | up to 1 year | 
| Disease control rate(DCR) | The rate of complete response(CR), partial response(PR) and stable disease(SD) assessed according to RANO criteria. | up to 1 year | 
| Overall survival(OS) |  | up to 1 year |