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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03374943




Registration number
NCT03374943
Ethics application status
Date submitted
26/09/2017
Date registered
15/12/2017
Date last updated
4/11/2021

Titles & IDs
Public title
A Trial of KB004 in Patients With Glioblastoma
Scientific title
A Phase I Safety and Bioimaging Trial of KB004 in Patients With Glioblastoma
Secondary ID [1] 0 0
ONJ2017-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KB004

Experimental: KB004 dose escalation - Patients will be entered at each KB004 dose level sequentially until 3-6 patients are evaluable for safety. Three sequential cohorts are planned in this study (3.5mg/kg, 5.25 mg/kg, 7.9 mg/kg) Additional dose levels may be explored based on the emerging data in the study.


Treatment: Drugs: KB004
KB004 is a recombinant, non-fucosylated, IgG1? (human f-allotype) monoclonal antibody targeting the extracellular ligand binding domain of the EphA3 (ephrin receptor) tyrosine kinase
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With KB004 Treatment-Related Adverse Events as Assessed using CTCAE v4.0. To determine the maximum tolerated dose (MTD).
Timepoint [1] 0 0
0-24 months
Secondary outcome [1] 0 0
Biodistribution of 89Zr-KB004
Timepoint [1] 0 0
0-24 months
Secondary outcome [2] 0 0
Response rates following KB004 infusion
Timepoint [2] 0 0
0-24 months
Secondary outcome [3] 0 0
Plasma concentration versus time (Serum half life) of 89Zr-KB004
Timepoint [3] 0 0
0-43 days
Secondary outcome [4] 0 0
Cmax of 89Zr-KB004
Timepoint [4] 0 0
0-43 days

Eligibility
Key inclusion criteria
- Adults (greater than or equal to 18 years of age) with histologically proven
glioblastoma

- Evidence of progressive glioblastoma (if within 3 months of radiotherapy, then
progression outside of radiotherapy field is required)

- Measurable disease by RANO (Response Assessment in Neuro-Oncology Criteria)

- ECOG (Eastern Cooperative Oncology Group score) 0 to 1

- Expected survival more than 3 months

- Steroid dose less than 2.5 mg per day dexamethasone equivalents and stable or reducing
for 1 week prior to day 1

- Archived (formalin fixed paraffin embedded) tissue or frozen tumour tissue or consent
to obtain a fresh tumour biopsy at enrolment is required.

- Adequate organ function. Out of range values that are not clinically significant will
be permitted, except for the following laboratory parameters which must be within the
ranges specified

- Neutrophils greater than or equal to 1.5 x 109 per L

- Platelets greater than or equal to 100 x 109 per L

- International Normalised Ratio less than or equal to 1.4

- Serum Aspartate aminotransferase and Alanine aminotransferase less than or equal to
2.5 x ULN (upper limit of normal)

- Serum bilirubin less than or equal to 1.5 x ULN (upper limit of normal)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Evidence of infratentorial, extracranial or leptomeningeal disease

- More than one prior systemic therapy for progressive disease or prior Steriotactic
radiosurgery (SRS) to sites of GB (glioblastoma).

- Prior treatment with bevacizumab or gliadel wafers

- Evidence of current or prior intracranial hemorrhage

- Need for anti-platelet or anti-coagulant drugs

- Use of anti-cancer therapy including craniotomy, chemotherapy, immunotherapy,
radiotherapy, or any investigational therapy within 28 days prior to Study Day 1

- History of major immunologic reaction to any immunoglobulin G containing agent

- Medical conditions which place the subject at an unacceptably high risk

- Subject is pregnant, lactating or unwilling or unable to use adequate contraception

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/12/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/09/2021
Sample size
Target
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [2] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
3078 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Olivia Newton-John Cancer Research Institute
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Humanigen, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a study of drug KB004 in patients with recurrent glioblastoma (GBM). Eligible
patients with measurable tumours will receive an initial trace (5mg) dose of zirconium
labelled KB004 (89ZrKB004) on day 1 followed by sequential Positron emission tomography (PET)
imaging over 1 week to determine its biodistribution into GBM and normal tissues. Safety
assessments and pharmacokinetic (movement of drug) sampling will also be undertaken over this
time. On Day 8, patients commence weekly KB004 infusions over 2 hours with standard
premedications. Three cohorts are planned in this study (3.5mg/kg, 5.25 mg/kg, 7.9 mg/kg;
additional dose levels may be explored based on toxicity, efficacy and biodistribution data
as determined by the safety monitoring committee). On day 36, patients receive both 89ZrKB004
and KB004, allowing assessment of receptor occupancy to guide recommended phase two dose
(RPTD) determination. Response rate (RANO) and survival data will be collected and patients
benefiting may continue KB004 treatment until disease progression. Primary objective: to
determine the toxicity and recommended phase two dose (RPTD) of KB004 in patients with
advanced Glioblastoma (GBM).

Secondary objectives: to determine the biodistribution and pharmacokinetics of 89ZrKB004; to
determine frequency of EphA3 (ephrin receptor A3) positive glioblastoma in archival specimens
and by 89ZrKB004 scans, and correlate with known biomarkers; to describe response rates per
RANO criteria (Response Assessment in Neuro-Oncology Criteria) and pharmacodynamics following
KB004 infusion; Exploratory objectives: to perform exploratory analysis between clinical
outcomes and biodistribution/Pharmacokinetics (PK)/pharmacodynamics (PD) data, including from
matched biopsies.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03374943
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Hui Gan
Address 0 0
Austin Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03374943