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

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

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A patient who is withdrawn from the study before the completion of the 1st cycle can be replaced with another patient.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.

Study Overview

• Status: Completed
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Drug: TTAC-0001

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; 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; Calculated amount of drug will be diluted with normal saline and administered intravenously.; Other Names: Tanibirumab
EXPERIMENTAL: Cohort 2; 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; Calculated amount of drug will be diluted with normal saline and administered intravenously.; Other Names: Tanibirumab
EXPERIMENTAL: Cohort 3; Patients will be treated with 12mg/kg of TTAC-0001 weekly in every 4 weeks of cycle.	Drug: TTAC-0001; Calculated amount of drug will be diluted with normal saline and administered intravenously.; Other Names: Tanibirumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the concentration-time curve (AUC)	Pharmacokinetics profile	up to 1 year
Maximum plasma concentration (Cmax)	Pharmacokinetics profile	up to 1 year
Minimum plasma concentration (Cmin)	Pharmacokinetics profile	up to 1 year
Clearance (CL)	Pharmacokinetics profile	up to 1 year
Volume of distribution (Vd)	Pharmacokinetics profile	up to 1 year
Half-life (t1/2)	Pharmacokinetics profile	up to 1 year
Angiogenic factors in serum or changes in concentration	Pharmacodynamics profile	up to 1 year
Perfusion parameter assessed by DCE-MRI	Pharmacodynamics profile	every 2 cycles(each cycle is 4 weeks), up to 1year
Expression of angiogenic factors in endothelial cells	Analyzed by IHC of tumor tissue	At screening
Immunogenicity	Anti-drug (TTAC-0001) antibody (ADA) test for evaluation of immunogenicity	Day 1 of every cycle(each cycle is 4 weeks), up to 1 year

Collaborators and Investigators

• Sponsor: PharmAbcine

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 4, 2016
• Primary Completion (ACTUAL): June 2, 2017
• Study Completion (ACTUAL): June 2, 2017

Study Registration Dates

• First Submitted: January 9, 2017
• First Submitted That Met QC Criteria: January 25, 2017
• First Posted (ESTIMATE): January 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: PMC_TTAC-0001_02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED