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A Trial of KB004 in Patients With Glioblastoma

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

 No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

 Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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)

    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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

 NCT03374943
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

 Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

 Olivia Newton-John Cancer Research Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

 Hui Gan
Principal Investigator Affiliation Austin Health
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

 Other, Industry
Overall Status Recruiting
Countries Australia
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

 Glioblastoma
Arms & Interventions

Arms

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.

Interventions

Drug: - KB004

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia

Status

Not yet recruiting

Address

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029

Site Contact

Po-ling Inglis

Po-ling.inglis@health.qld.gov.au

+6173646 8111

Austin Health, Heidelberg, Victoria, Australia

Status

Recruiting

Address

Austin Health

Heidelberg, Victoria, 3078

Site Contact

Gan Hui, MBBS, PhD

hui.gan@austin.org.au

+61394969925

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