GlioblastomaPhase 1NCT03374943

A Trial of KB004 in Patients With Glioblastoma

A Phase 1 study testing KB004 in people with Glioblastoma, run by Olivia Newton-John Cancer Research Institute at 2 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioblastoma
What is being tested?: KB004
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 2 sitesAustralia
Study dates: 5 Dec 2017to 22 Sep 2021
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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)

Who cannot join

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

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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

Trial locations and contacts

2 sites in 1 country.

Australia2 sites

Royal Brisbane and Women's Hospital
Brisbane, Queensland, 4029
Austin Health
Heidelberg, Victoria, 3078

Other trials in Australia

About this study

Official title: A Phase I Safety and Bioimaging Trial of KB004 in Patients With Glioblastoma

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.

Conditions: Glioblastoma
Being tested: KB004
Medical subject headings: Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KB004Drug
KB004 is a recombinant, non-fucosylated, IgG1κ (human f-allotype) monoclonal antibody targeting the extracellular ligand binding domain of the EphA3 (ephrin receptor) tyrosine kinase

Study groups in NCT03374943
Study group	Role	What they receive
KB004 dose escalation	Experimental	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. Receives: Drug: KB004

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With KB004 Treatment-Related Adverse Events as Assessed using CTCAE v4.0. To determine the maximum tolerated dose (MTD).
Three patients are recruited per dose level, 3 dose levels. Dose limiting toxicity (DLT) defined as Grade 4 neutropenia > 7 day duration Grade 3 or 4 febrile neutropenia Grade 3 or 4 thrombocytopenia > 7 day duration Grade 4 anaemia > 7 day duration Grade 3 or 4 non-hematologic adverse events which do not resolve within 48 hours with maximal supportive care.
Grade 4 or recurrent Grade 3 infusion reactions despite maximal supportive care and dose reductions Significant intracranial haemorrhage not reasonably attributed to other cause More than 14 days of treatment delay due to attributable toxicity Other toxicities as determined by the investigators. In the absence of any dose limiting toxicity in a cohort, escalate to the next dose level. If one DLT is seen in the first three patients of a cohort, an additional three patients will be recruited to that cohort. If two or more DLT's are seen in any cohort, that cohort will be deemed the maximum tolerated dose.
Measured: 0-24 months

Secondary outcomes (4)

Biodistribution of 89Zr-KB004
Eligible patients with measurable tumours will receive an initial trace (5mg) dose of zirconium labelled KB004 (89Zr-KB004) on day 1 followed by sequential Positron emission tomography, or PET imaging over 1 week to determine its biodistribution into GBM and normal tissues, frequency of EphA3 (ephrin type-A receptor 3) expression in glioblastoma (GBM) and quantitative tumor antibody uptake.
Measured: 0-24 months
Response rates following KB004 infusion
Response Assessment in Neuro-Oncology criteria will be used to interpret MRI (magnetic resonance imaging) scans
Measured: 0-24 months
Plasma concentration versus time (Serum half life) of 89Zr-KB004
Pharmacokinetics (plasma concentration versus time) of 89Zr-KB004 will be determined using gamma well counting of the Zirconium in the samples at various timepoints-Day 1 89Zr-KB004 infusion: pre-infusion, 5min, 1 hour, 2 hours, 4 hours and 24 hours post infusion, then Day 3 or 4, 6 or 7. PK (Pharmacokinetics) timepoints Day 89Zr-KB004 infusion: pre-infusion, 5min, 1 hour, 2 hours, 4 hours and 24 hours post infusion then Day 39 or 40 and Day 42 or 43.
Measured: 0-43 days
Cmax of 89Zr-KB004
Pharmacokinetics (Cmax) of 89Zr-KB004 will be determined using gamma well counting of the Zirconium in the samples at various timepoints-Day 1 89Zr-KB004 infusion: pre-infusion, 5min, 1 hour, 2 hours, 4 hours and 24 hours post infusion, then Day 3 or 4, 6 or 7. PK (Pharmacokinetics) timepoints Day 89Zr-KB004 infusion: pre-infusion, 5min, 1 hour, 2 hours, 4 hours and 24 hours post infusion then Day 39 or 40 and Day 42 or 43.
Measured: 0-43 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Dec 201722 Sep 2021

First posted15 Dec 2017
Study start5 Dec 2017
Primary completion25 Jan 2021
Study completion22 Sep 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for GlioblastomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Model description: The study will use a 3+3 methodology for the 3 dose levels proposed. In brief, three patients will be recruited per dose level. In the absence of any Dose Limiting toxicity (DLT) in a cohort, escalation to the next dose level will occur.
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03374943
Sponsor's protocol ID: ONJ2017-002
Status last verified: Nov 2021
First submitted: 26 Sep 2017
Last updated: 4 Nov 2021
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
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RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
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RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

All Glioblastoma trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Safety and Bioimaging Trial of KB004 in Patients With Glioblastoma
ClinicalTrials.gov ID: NCT03374943
Acronym / sponsor ID: ONJ2017-002
Conditions: Glioblastoma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Olivia Newton-John Cancer Research InstituteUniversity, hospital or other
Collaborators: Humanigen, Inc.
Study start: 5 Dec 2017 (actual)
Primary completion: 25 Jan 2021 (actual)
Study completion: 22 Sep 2021 (actual)
First posted: 15 Dec 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: The study will use a 3+3 methodology for the 3 dose levels proposed. In brief, three patients will be recruited per dose level. In the absence of any Dose Limiting toxicity (DLT) in a cohort, escalation to the next dose level will occur.

Arm	Type	Receives
KB004 dose escalation	Experimental	Drug: KB004Patients 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KB004KB004 is a recombinant, non-fucosylated, IgG1κ (human f-allotype) monoclonal antibody targeting the extracellular ligand binding domain of the EphA3 (ephrin receptor) tyrosine kinase	Drug	KB004 dose escalation

Primary outcome

Number of Participants With KB004 Treatment-Related Adverse Events as Assessed using CTCAE v4.0. To determine the maximum tolerated dose (MTD).
Time frame: 0-24 months
Three patients are recruited per dose level, 3 dose levels. Dose limiting toxicity (DLT) defined as Grade 4 neutropenia > 7 day duration Grade 3 or 4 febrile neutropenia Grade 3 or 4 thrombocytopenia > 7 day duration Grade 4 anaemia > 7 day duration Grade 3 or 4 non-hematologic adverse events which do not resolve within 48 hours with maximal supportive care. Grade 4 or recurrent Grade 3 infusion reactions despite maximal supportive care and dose reductions Significant intracranial haemorrhage not reasonably attributed to other cause More than 14 days of treatment delay due to attributable toxicity Other toxicities as determined by the investigators. In the absence of any dose limiting toxicity in a cohort, escalate to the next dose level. If one DLT is seen in the first three patients of a cohort, an additional three patients will be recruited to that cohort. If two or more DLT's are seen in any cohort, that cohort will be deemed the maximum tolerated dose.

4 secondary outcomes

Biodistribution of 89Zr-KB004
Time frame: 0-24 months
Response rates following KB004 infusion
Time frame: 0-24 months
Plasma concentration versus time (Serum half life) of 89Zr-KB004
Time frame: 0-43 days
Cmax of 89Zr-KB004
Time frame: 0-43 days

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
Individual participant dataSharing planned: No

Related trials for Glioblastoma

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Hui Gan principal investigator

Austin Health

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KB004 in people with Glioblastoma, run by Olivia Newton-John Cancer Research Institute at 2 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With KB004 Treatment-Related Adverse Events as Assessed using CTCAE v4.0. To determine the maximum tolerated dose (MTD). (time frame: 0-24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03374943.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.