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Trial registered on ANZCTR


Registration number
ACTRN12615001156572
Ethics application status
Approved
Date submitted
18/08/2015
Date registered
29/10/2015
Date last updated
2/04/2019
Date data sharing statement initially provided
2/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Open Label Study to Evaluate tanibirumab (TTAC-001) in Patients with Recurrent Glioblastoma
Scientific title
A Multicenter, 3-Arm, Open-Label, Phase 2a Clinical Trial to Evaluate the Safety and Efficacy of TTAC-0001, a Fully Human Monoclonal Antibody in Patients with Recurrent Glioblastoma
Secondary ID [1] 287289 0
PMC_TTAC-0001_02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 295926 0
Condition category
Condition code
Cancer 296186 296186 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
3 treatment arms:
Arm 1 - (tanibirumab 8 mg/kg days 1, 8, 15 /4 weeks): 1 intravenous infusion/week, 3 infusions per cycle and 1 week observation. Treatment period: maximum one year
Arm 2 - (tanibirumab 12mg/kg days 1, 8, 15 /4 weeks): 1 intravenous infusion/week, 3 infusions per cycle and 1 week observation. Treatment period: maximum one year
Arm 3 - (tanibirumab 12mg/kg weekly): 1 intravenous infusion/week, 4 infusions per cycle and no observation period. Treatment period: maximum one year
All doses will be administered at study sites.
Intervention code [1] 292609 0
Treatment: Drugs
Comparator / control treatment
NIL
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295852 0
Evaluate the safety of tanibirumab in patients with recurrent glioblastoma.
Adverse Events (AEs) are evaluated by considering the frequency and intensity (severity) of AEs and other abnormal findings of clinical tests recorded by patients. Information on AE, such as symptoms, start and stop dates, severity, the relationship to IP, relevant measures, treatment and results are recorded.
Known/possible adverse reactions include:
Very Common – Greater than 10% incidence; Hemangioma, Rash; Pruritus; Fatigue
Common – 1-10% incidence: Alopecia; Acne; Rash; Pyogenic granuloma; Mucosal inflammation – digestive, genital or urinary tract infections; Asthenia; Oedema ; Peripheral Oedema; Constipation; Diarrhoea; Nausea; Vomiting; Anaemia; Neutropenia: Decreased appetite; Headache; Flushing; Hypertension; Arthralgia; Myalgia; Hypersensitivity; Herpes; Infusion related reaction
Safety assessments include adverse event reporting by participants and investigators, physical examinations, vital signs measurement, laboratory tests, ECG, chest x-ray and immunogenicity
Timepoint [1] 295852 0
Adverse events will be assessed weekly during study treatment, termination visit and 14 days after termination visit.
Secondary outcome [1] 316722 0
To determine the dose-response of tanibirumab by tumour response evaluation in patients with recurrent glioblastoma.
MRI scan is used for lesion measurement for tumour response evaluation. CT scan can be used if necessary. Tumour evaluation will be performed every 8 weeks during study treatment and at the termination visit. The radiographic assessment will be combined with assessment of corticosteroid dosing and clinical status to assign an overall, integrated response in accordance with Response Assessment in Neuro-oncology (RANO) criteria.
Timepoint [1] 316722 0
Tumour response is assessed at the end of every 2nd cycle
Secondary outcome [2] 316934 0
PK parameters
1) Area under the concentration-time curve (AUC)
2) Maximum plasma concentration (Cmax)
3) Minimum plasma concentration (Cmin)
4) Clearance (CL)
5) Volume of distribution (Vd)
6) Half-life (t1/2).
Timepoint [2] 316934 0
Pharmacokinetic (PK) samples will be collected at Cycle 1, day 1, 8, 15, 29 and day 1 of repeat cycles. Drug concentration will be analysed.
Secondary outcome [3] 316935 0
To evaluate Pharmacodynamic (PD) parameters by clinical biomarker test
Timepoint [3] 316935 0
Pharmacodynamic (PD) samples will be collected prior to administration of the investigational drug at day 1 of every cycle and termination visit. Angiogenic factors in the serum or changes in the concentration of receptors (VEGF, PlGF, sVEGFR-2, sVEGFR-1, and sTie-2) will be analysed

Eligibility
Key inclusion criteria
1. Both male and female patients at least 19 years old
2. 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.
3. At least one confirmed measurable lesion or non measurable lesion by response assessment in neuro-oncology (RANO) criteria
4. Karnofsky Performance Status (KPS) at least 80
5. A person who satisfies the following criteria in hematologic, renal, and hepatic function tests
a. Hematologic tests
Absolute neutrophil count (ANC) at least 1.5 x 109/L
Platelets at least 75 x 109/L
Hemoglobin at least 9.0 g/dL
b. Blood coagulation tests
Prothrombin time (PT) at least 1.5 x Upper limit of normal (UNL)
Activated partial thromboplastin Time (aPTT) at least 1.5 x UNL
c. Hepatic function tests
Total bilirubin at least 1.5 x UNL
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at least 3 x ULN
d. Renal function test
Creatinine clearance (CrCl) at least 30 mL/min
7. At least 12 weeks of expected survival time
8. Signed informed consent
Minimum age
19 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Diagnosed with malignant tumors, except basal cell carcinoma, cutaneous squamous cell carcinoma, and noninvasive uterine cervical cancer treated within 2 years prior to participating in the study.
2. The following concomitant diseases:
a. Uncontrolled hypertension (systolic blood pressure [SBP] greater than 150 or diastolic blood pressure [DBP] greater than 90 mmHg)
b. Uncontrolled seizures
c. Class III or IV heart failure by New York Heart Association (NYHA) classification
d. Oxygen-dependent chronic disease
e. Active psychiatric disorder (schizophrenia, major depressive disorder, bipolar disorder etc.). Treated depression with ongoing antidepressant medication is not an exclusion.
3. Not recovered below National Cancer Institute –Common Terminology for Adverse Events (NCI-CTCAE) grade 2 from AEs due to CCRT
4. Treatment with systemic chemotherapy, hormonal therapy, immunotherapy or biologic therapy except CCRT or temozolomide alone within 2 weeks prior to the baseline visit
5. Undergone major surgery requiring general anesthesia or a respiratory assistance device within 4 weeks prior to the baseline visit (within 2 weeks for video-assisted thoracoscopic surgery [VATS] or open-and-closed [ONC] surgery)
6. Treated with other investigational drugs within 4 weeks prior to the baseline visit for this study
7. Pregnant or lactating females, and females/males of childbearing potential who don't agree to a reliable and adequate method of contraception [Hormonal contraceptives such as the combined oral contraceptive pill; intrauterine devices or the implantation of intrauterine system (IUD); blockage methods (condoms, diaphragms, vaginal sponges, cervical cap); sterilization surgery such as tubal ligation in females and vasectomy in males.
8. A known history of severe drug hypersensitivity or hypersensitivity to a therapy similar to the study drug
9. Unable to participate in the trial according to the investigator’s decision.
10. Previous therapy with vascular endothelial growth factor (VEGF)-targeted agents including (but not limited to) bevacizumab

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
An enrolment criterion to the next arm is defined as no patients in the previous treatment arm showing grade 3 or above of haemangioma or other Dose Limiting Toxicities (DLT) during the 1st cycle. A safety review committee (SRC) will convene to determine the patient’s safety with a decision on enrolment into the next arm or change in dosing frequency of study drug in the case of occurrence of grade 3 or above of haemangioma or other DLTs during the 1st cycle
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
This study will start with enrolment of participants into the 1st arm; thereafter participants will be sequentially enrolled into the 2nd and 3rd arm when the safety from the 1st arm is established.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Demographic data:
Descriptive statistics (mean, standard deviation [SD}, frequency, rate, etc.) in accordance with the characteristics of the data will be provided.
Safety evaluation:
The safety will be evaluated in all patients who are treated with at least one dose of the investigational drug. Descriptive statistics (the number of patients, the incidence, and the number of events) by treatment arm will be provided for treatment-emergent adverse event (TEAE), an adverse drug reaction (ADR) and a serious adverse event (SAE).
The AEs occurring after administration of the study drug will be coded according to System Organ Class (SOC) and Preferred Term (PT) by using a medical dictionary for regulatory activities (MedDRA), and detailed information about the AEs will be provided by treatment arm.
Descriptive statistics (mean, SD, frequency, rate etc.) in accordance with the characteristics of data will be provided for vital signs, laboratory tests, ECG, chest X-ray, and immunogenicity.
Efficacy evaluation:
A rate and 95% confidence interval for 6 months PFS using the Kaplan-Meier method will be determined. Median survival time and its 95% confidence interval for OS using the Kaplan-Meier method will also be determined. ORR and DCR will be calculated, and two-sided 95% confidence interval will be presented.
This study is an exploratory study to evaluate the safety and dose-response of TTAC-0001 in patients with recurrent glioblastoma. The study is planned to recruit a total of 12 patients, 3 patients for the 1st arm and 2nd arm, respectively and 6 patients for 3rd arm. No formal sample size calculations have been performed.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/02/2016
Actual
8/02/2016
Date of last participant enrolment
Anticipated
1/06/2016
Actual
7/09/2016
Date of last data collection
Anticipated
31/10/2017
Actual
5/12/2017
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment hospital [1] 4201 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 4202 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 10112 0
6009 - Nedlands
Recruitment postcode(s) [2] 10113 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 291846 0
Commercial sector/Industry
Name [1] 291846 0
PharmAbcine Inc.
Country [1] 291846 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
PharmAbcine Inc.
Address
461-8 Jeonmin-Dong
Yuseong-Gu, Daejeon
Country
Korea, Republic Of
Secondary sponsor category [1] 290800 0
None
Name [1] 290800 0
Address [1] 290800 0
Country [1] 290800 0
Other collaborator category [1] 278592 0
Commercial sector/Industry
Name [1] 278592 0
Novotech (Australia) Pty Limited
Address [1] 278592 0
Level 3 / 235 Pyrmont Street,
Pyrmont NSW 2009
Country [1] 278592 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293362 0
Sir Charles Gairdner Hospital Group Human Research Ethics Committee
Ethics committee address [1] 293362 0
Sir Charles Gairdner Hospital,
2nd Floor, A Block
Hospital Avenue
Nedlands WA 6009
Ethics committee country [1] 293362 0
Australia
Date submitted for ethics approval [1] 293362 0
28/07/2015
Approval date [1] 293362 0
06/10/2015
Ethics approval number [1] 293362 0
Ethics committee name [2] 293363 0
Austin Health Human Research Ethics Committee
Ethics committee address [2] 293363 0
Austin Health
145 Studley Road
Heidelberg
Victoria
Australia, 3084
Ethics committee country [2] 293363 0
Australia
Date submitted for ethics approval [2] 293363 0
05/08/2015
Approval date [2] 293363 0
17/11/2015
Ethics approval number [2] 293363 0

Summary
Brief summary
The primary purpose of this study is to evaluate the safety and efficacy of tanibirumab in participants with recurrent glioblastoma multiforme (GBM).
Who is it for?
You may be eligible to join this study if you are aged 19 or over, and have been diagnosed with recurrent GBM following treatment with temozolomide chemotherapy with radiotherapy.
Study details
Tumour angiogenesis is the process that leads to the formation of blood vessels in a tumour, which in turn support cancer cell survival, local tumour growth, and the development of distant metastasis. The investigational drug tanibirumab (TTAC-0001) interferes with the angiogenesis process, inhibiting the formation of the blood vessels and thereby starving the tumour cells of the nutrients and oxygen required for growth. Participants in this study will be enrolled sequentially to arm 1, 2 or 3 with participants enrolled to arm 2 and 3 only after a safety evaluation of the previous arm. Each patient will only be allocated to one arm depending on the time of enrolment. All participants will receive tanibirumab in 3 or 4 doses, one per week, per cycle, for a total of up to 1 year, disease progression or study withdrawal.

Throughout the study safety will be assessed by monitoring and assessment of adverse events, vital signs, laboratory tests including testing for immunogenicity (the ability of the study drug to provoke an immune response). Tumour response will be assessed by evaluating MRI scans performed every 8 weeks during treatment and at treatment termination. Blood sampling for drug interaction and distribution within the body will also be collected.
It is hoped that the findings of this trial will develop our understanding of the safety of tanibirumab and of it's efficacy as a potential drug treatment for recurrent glioblastoma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59582 0
Dr Anna Nowak
Address 59582 0
Comprehensive Cancer Centre
Level 1, DD Block
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6009
Country 59582 0
Australia
Phone 59582 0
+61 (0)8 6383 3180
Fax 59582 0
Email 59582 0
[email protected]
Contact person for public queries
Name 59583 0
Seon Young Lee
Address 59583 0
PharmAbcine, Inc.
461-8 Jeonmin-Dong
Yuseong-Gu, Daejeon,
Country 59583 0
Korea, Republic Of
Phone 59583 0
+82-42-863-2017
Fax 59583 0
Email 59583 0
[email protected]
Contact person for scientific queries
Name 59584 0
Weon Sup Lee
Address 59584 0
PharmAbcine, Inc.
461-8 Jeonmin-Dong
Yuseong-Gu, Daejeon,
Country 59584 0
Korea, Republic Of
Phone 59584 0
+82-42-863-2017
Fax 59584 0
Email 59584 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not Applicable


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.