Solid TumoursPhase 1ECRESTNCT02687386
A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR
A Phase 1 study of Solid Tumours and CNS Tumours, run by Dr David Ziegler at 2 sites in Australia.
Trial summary
This is an open-label, sequential dose exploration study of single agent EEDVSMit administered by intravenous (IV) infusion twice weekly, followed by weekly maintenance dosing, in children with recurrent/refractory solid or CNS tumours. Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Solid Tumours, CNS Tumours
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesAustralia
- Study dates
- 8 Feb 2016to 29 Dec 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 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be ≥ 2 years and ≤ 21 years old at the time of study enrolment.
- Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age
- Patients must have relapsed or refractory solid or CNS tumours or have a diagnosis of DIPG. Patients must have had histologic verification of malignancy at original diagnosis or relapse, or a diagnosis of DIPG by MRI imaging.
- Patients must have either measurable or evaluable disease for Part B of the study only
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Who cannot join
- Pregnant or breast-feeding women will not be entered on this study.
- Any active uncontrolled infection
- Patients who are known to be serologically positive for Hepatitis A, B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis.
- Known positive test for human immunodeficiency virus infection
- Patients with disease of any major organ system that would compromise their ability to withstand therapy
- Concurrent or prior (within 7 days of enrolment) anticoagulation therapy, except low molecular weight heparins or low dose aspirin
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- Patients receiving corticosteroids must be on a stable dose that has not been increased for at least 7 days prior to study enrolment.
- Patients who are currently receiving another investigational drug are ineligible.
- Patients who are currently receiving other antineoplastic agents are ineligible.
- All herbal supplements, vitamins, and nutritional supplements taken within the last 30 days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed and approved by the Study Chair.
- Patient will not be available for protocol-required study visits or procedures, to the best of the subject/parent/guardian's and investigator's knowledge.
- Patient has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject/parent/guardian to give written informed consent and/or to comply with all required study procedures.
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- Patients will be screened for antibodies to S. typhimurium and will not be eligible until antibodies are non-detectable
- Patients will be screened for IL6 and TNFa cytokines and will not be eligible until levels are less than 3x times the detectable limit of the assay.
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
Sydney Children's Hospital
Randwick, New South Wales, 2031
The Children's Hospital at Westmead
Westmead, New South Wales
About this study
Official title: A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT (EEDVsMit) in Children With Recurrent / Refractory Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor (EGFR) (ECREST Study)
This is an open-label, sequential dose exploration study of single agent EEDVSMit administered by intravenous (IV) infusion twice weekly, followed by weekly maintenance dosing, in children with recurrent/refractory solid or CNS tumours.
Read the detailed description
Eligible subjects enrolled in the study will receive EEDVSMit by IV injection twice weekly as a 20 min infusion beginning at study day 1 for the first cycle (4 weeks) then weekly for subsequent cycles. Subjects will undergo radiological assessment of their tumours after the first cycle, and every second cycle thereafter. Dosing with EEDVSmit will continue unless there is radiographic evidence of progressive disease (PD) per RECIST criteria version 1.1, the subject becomes intolerant to the study medication, signs and symptoms of clinical progression are evident as determined by the principal investigator, or the subject/parent/guardian withdraws consent. Suspected tumour progression should be confirmed with a repeat scan after 4 weeks to exclude the possibility of pseudoprogression.
Determination of EGFR expression for eligibility of subjects will be assessed at the local site. In addition, radiological assessment confirming measurable disease by the RECIST criteria is also required for entry into the Part B of the study.
The study will be conducted in two parts: Part A -Dose Exploration and Part B -Dose Expansion.
Part A - Dose Exploration:
The dose exploration part of the study is aimed at determining a recommended phase 2 dose (RP2D) in this patient group. A standard dose escalation with a rolling 6 design will be used.
Part A will commence dosing at one log scale below the maximum dose tested in the recent adult recurrent glioma trial (with the first 4 doses administered at 1/10 of the starting dose) and escalate to a maximum of 8x109 EEDVSMit evaluating the safety and tolerability, of EEDVSMit. The first 4 doses administered will be reduced by a further log reduction.
Part B - Dose expansion:
The dose expansion phase (Part B) will begin upon completion of the dose exploration (Part A). Up to 12 subjects with recurrent/refractory solid or CNS tumours will be treated at the Recommended Phase Two Dose (RPTD). All doses, including the first 4, will be at the same dose level established in Part A (RPTD).
- Conditions
- Solid Tumours, CNS Tumours
- Being tested
- Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)
- Keywords
- Recurrent, Refractory
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)Drug
Also called EDV also stands for EnGeneIC Dream Vector
EnGeneIC Delivery Vehicles (EDVs) are nanocells which can be loaded with anti-cancer drugs (mitoxantrone in this study) and targeted to tumor cells. These bacterially-derived nanocells are coated in bispecific antibodies (BsAb) that recognize oncogenic receptors on the tumor cell surface. Once bound to the tumour cell, the targeted and drug-loaded EDVs are endocytosed and release their toxic payload to destroy the tumor cell.
| Study group | Role | What they receive |
|---|---|---|
| Mitoxantrone packaged EDV | Experimental | Mitoxantrone packaged EDV (EnGeneIC Dream Vector) Receives: Drug: Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle) |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD at which fewer than one third of patients experience dose limiting toxicity as assessed by CTCAE v4.0
To determine a recommended phase 2 dose (RP2D) for EEDVsMit administered intravenously in children with recurrent / refractory solid or CNS tumours expressing EGFR
Measured: Day 28 (cycle 1)
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
To define and describe the toxicities of EEDVSMit administered on these schedules in children with recurrent/refractory solid or CNS tumours
Measured: Up to 35 days after the completion of study treatment
Incidence of all adverse events as assessed by CTCAE v4.0, clinically significant changes in vital signs, ECGs and clinical laboratory tests
Assess the safety and tolerability of EEDVSMit in children with recurrent/refractory solid or CNS tumours.
Measured: Up to 35 days after the completion of study treatment
Secondary outcomes (3)
Assess disease response according to RECIST version 1.1 for children with recurrent/refractory solid or CNS tumours
To preliminarily define the anti-tumour activity of EEDVSMit and assess response rates using RECIST version 1.1 criteria in children with recurrent/refractory solid or CNS tumours within the confines of a phase 1 study.
Measured: Up to 35 days after the completion of study treatment
Assess overall survival
Assess overall survival (OS) in children with recurrent/refractory solid or CNS tumours treated with EEDVSMit on this schedule
Measured: 12 months from the date the last subject was enrolled in the study.
Time to response assessed by radiological imaging and RECIST v1.1
Estimate the time to response.
Measured: Evaluated at Day 56 (after cycle 2), then every second cycle to the end of study treatment (up to 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2016 (estimated)
- Study start8 Feb 2016
- Primary completion29 Dec 2021
- Study completion29 Dec 2021
Why it stopped: Study medication no longer in production
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumoursStudies 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
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr David Ziegler
- Sponsor type
- University, hospital or other
- Collaborators
- Engeneic Pty Limited
- Responsible party
- Sponsor-investigator, Dr David Ziegler, Sydney Children's Hospitals Network
- Investigators
- David Ziegler, MBBS, Study chair, Sydney Children's Hospitals Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02687386
- Sponsor's protocol ID
- KCA001
- Acronym
- ECREST
- Status last verified
- Jan 2022
- First submitted
- 28 Jan 2016
- Last updated
- 14 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: De-identified data is planned to be shared with EnGeneIC.
Publications
Evans L, Walker R, MacDiarmid J, Brahmbhatt H, Anazodo A, McCowage G, Gifford AJ, Kavallaris M, Trahair T, Ziegler DS. A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT in Children with Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor. Target Oncol. 2024 May;19(3):333-342. doi: 10.1007/s11523-024-01051-2. Epub 2024 Mar 28.
PubMed 38546944
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT (EEDVsMit) in Children With Recurrent / Refractory Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor (EGFR) (ECREST Study)
- ClinicalTrials.gov ID
- NCT02687386
- Acronym / sponsor ID
- ECREST / KCA001
- Conditions
- Solid Tumours, CNS Tumours
- Keywords
- Recurrent, Refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study medication no longer in production
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Dr David ZieglerUniversity, hospital or other
- Collaborators
- Engeneic Pty Limited
- Study start
- 8 Feb 2016 (actual)
- Primary completion
- 29 Dec 2021 (actual)
- Study completion
- 29 Dec 2021 (actual)
- First posted
- 22 Feb 2016 (estimated)
- 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.
This is an open-label, sequential dose exploration study of single agent EEDVSMit administered by intravenous (IV) infusion twice weekly, followed by weekly maintenance dosing, in children with recurrent/refractory solid or CNS tumours.
Detailed description
Eligible subjects enrolled in the study will receive EEDVSMit by IV injection twice weekly as a 20 min infusion beginning at study day 1 for the first cycle (4 weeks) then weekly for subsequent cycles. Subjects will undergo radiological assessment of their tumours after the first cycle, and every second cycle thereafter. Dosing with EEDVSmit will continue unless there is radiographic evidence of progressive disease (PD) per RECIST criteria version 1.1, the subject becomes intolerant to the study medication, signs and symptoms of clinical progression are evident as determined by the principal investigator, or the subject/parent/guardian withdraws consent. Suspected tumour progression should be confirmed with a repeat scan after 4 weeks to exclude the possibility of pseudoprogression.
Determination of EGFR expression for eligibility of subjects will be assessed at the local site. In addition, radiological assessment confirming measurable disease by the RECIST criteria is also required for entry into the Part B of the study.
The study will be conducted in two parts: Part A -Dose Exploration and Part B -Dose Expansion.
Part A - Dose Exploration:
The dose exploration part of the study is aimed at determining a recommended phase 2 dose (RP2D) in this patient group. A standard dose escalation with a rolling 6 design will be used.
Part A will commence dosing at one log scale below the maximum dose tested in the recent adult recurrent glioma trial (with the first 4 doses administered at 1/10 of the starting dose) and escalate to a maximum of 8x109 EEDVSMit evaluating the safety and tolerability, of EEDVSMit. The first 4 doses administered will be reduced by a further log reduction.
Part B - Dose expansion:
The dose expansion phase (Part B) will begin upon completion of the dose exploration (Part A). Up to 12 subjects with recurrent/refractory solid or CNS tumours will be treated at the Recommended Phase Two Dose (RPTD). All doses, including the first 4, will be at the same dose level established in Part A (RPTD).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mitoxantrone packaged EDV | Experimental | Drug: Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)Mitoxantrone packaged EDV (EnGeneIC Dream Vector) |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Patients must be ≥ 2 years and ≤ 21 years old at the time of study enrolment.
- Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age
- Patients must have relapsed or refractory solid or CNS tumours or have a diagnosis of DIPG. Patients must have had histologic verification of malignancy at original diagnosis or relapse, or a diagnosis of DIPG by MRI imaging.
- Patients must have either measurable or evaluable disease for Part B of the study only
- Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
Key exclusion criteria (15 listed)
- Pregnant or breast-feeding women will not be entered on this study.
- Any active uncontrolled infection
- Patients who are known to be serologically positive for Hepatitis A, B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis.
- Known positive test for human immunodeficiency virus infection
- Patients with disease of any major organ system that would compromise their ability to withstand therapy
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 |
|---|---|---|
| Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)Also: EDV also stands for EnGeneIC Dream VectorEnGeneIC Delivery Vehicles (EDVs) are nanocells which can be loaded with anti-cancer drugs (mitoxantrone in this study) and targeted to tumor cells. These bacterially-derived nanocells are coated in bispecific antibodies (BsAb) that recognize oncogenic receptors on the tumor cell surface. Once bound to the tumour cell, the targeted and drug-loaded EDVs are endocytosed and release their toxic payload to destroy the tumor cell. | Drug | Mitoxantrone packaged EDV |
Primary outcome
MTD at which fewer than one third of patients experience dose limiting toxicity as assessed by CTCAE v4.0
Time frame: Day 28 (cycle 1)
To determine a recommended phase 2 dose (RP2D) for EEDVsMit administered intravenously in children with recurrent / refractory solid or CNS tumours expressing EGFR
Incidence of treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Up to 35 days after the completion of study treatment
To define and describe the toxicities of EEDVSMit administered on these schedules in children with recurrent/refractory solid or CNS tumours
Incidence of all adverse events as assessed by CTCAE v4.0, clinically significant changes in vital signs, ECGs and clinical laboratory tests
Time frame: Up to 35 days after the completion of study treatment
Assess the safety and tolerability of EEDVSMit in children with recurrent/refractory solid or CNS tumours.
3 secondary outcomes
Assess disease response according to RECIST version 1.1 for children with recurrent/refractory solid or CNS tumours
Time frame: Up to 35 days after the completion of study treatment
Assess overall survival
Time frame: 12 months from the date the last subject was enrolled in the study.
Time to response assessed by radiological imaging and RECIST v1.1
Time frame: Evaluated at Day 56 (after cycle 2), then every second cycle to the end of study treatment (up to 12 months)
Results and safety
The study was stopped early (reason given: Study medication no longer in production). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2022.
- Derived from this study: PubMed 38546944Evans L, Walker R, MacDiarmid J, Brahmbhatt H, Anazodo A, McCowage G, Gifford AJ, Kavallaris M, Trahair T, Ziegler DS. A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT in Children with Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor. Target Oncol. 2024 May;19(3):333-342. doi: 10.1007/s11523-024-01051-2. Epub 2024 Mar 28.
- Individual participant dataSharing planned: Undecided. De-identified data is planned to be shared with EnGeneIC.
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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.
David Ziegler, MBBS study chair
Sydney Children's Hospitals Network
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 of Solid Tumours and CNS Tumours, run by Dr David Ziegler 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 6 inclusion and 15 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: stopped early, as of the sponsor's last update on 14 Feb 2022. 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 was stopped early (reason given: Study medication no longer in production). Results are not available in the source record.
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?
MTD at which fewer than one third of patients experience dose limiting toxicity as assessed by CTCAE v4.0 (time frame: Day 28 (cycle 1)). The study lists 3 primary outcomes in all. 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 NCT02687386, which also lists 1 linked publication.
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 14 Feb 2022.