Recurrent Glioblastoma
Conditions
Brief summary
Study Design - Multicenter, open-label, 3 arms, stepwise, phase Ⅱa clinical trial Study objective: 1. Primary - To evaluate the safety of TTAC-0001 in patients with recurrent glioblastoma. 2. Secondary - To determine the efficacy of TTAC-0001 in patients with recurrent glioblastoma. 3. 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 A patient who is withdrawn from the study before the completion of the 1st cycle can be replaced with another patient.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.
Interventions
DRUGTTAC-0001
Calculated amount of drug will be diluted with normal saline and administered intravenously.
Sponsors
PharmAbcine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events | up to 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS at 6-month time point | 6 months | — |
| Objective response rate (ORR) | up to 1 year | The rate of complete response and partial response assessed according to RANO criteria. |
| Disease control rate(DCR) | up to 1 year | The rate of complete response(CR), partial response(PR) and stable disease(SD) assessed according to RANO criteria. |
| Overall survival(OS) | up to 1 year | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Half-life (t1/2) | up to 1 year | Pharmacokinetics profile |
| Angiogenic factors in serum or changes in concentration | up to 1 year | Pharmacodynamics profile |
| Area under the concentration-time curve (AUC) | up to 1 year | Pharmacokinetics profile |
| Expression of angiogenic factors in endothelial cells | At screening | Analyzed by IHC of tumor tissue |
| Immunogenicity | Day 1 of every cycle(each cycle is 4 weeks), up to 1 year | Anti-drug (TTAC-0001) antibody (ADA) test for evaluation of immunogenicity |
| Perfusion parameter assessed by DCE-MRI | every 2 cycles(each cycle is 4 weeks), up to 1year | Pharmacodynamics profile |
| Maximum plasma concentration (Cmax) | up to 1 year | Pharmacokinetics profile |
| Minimum plasma concentration (Cmin) | up to 1 year | Pharmacokinetics profile |
| Clearance (CL) | up to 1 year | Pharmacokinetics profile |
| Volume of distribution (Vd) | up to 1 year | Pharmacokinetics profile |
Outcome results
None listed