ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12626001157369

Ethics application status

Approved

Date submitted

25/05/2026

Date registered

17/09/2026

Date last updated

17/09/2026

Date data sharing statement initially provided

17/09/2026

Type of registration

Prospectively registered

Titles & IDs

Public title

EphA2 Chimeric Antigen Receptor (CAR) T cell Therapy for Children with Bone Tumours: A Phase I Clinical Trial

Scientific title

EphA2 Chimeric Antigen Receptor (CAR) T cell Therapy for Children with Bone Tumours: A Phase I Clinical Trial

Additional trial identifiers [1]

Universal Trial Number (UTN)

Trial acronym

E2CAR

Related trial records

Health condition

Health condition(s) studied:

Osteosarcoma

Ewing sarcoma

Condition category

Condition code

Cancer

Children's - Other

Cancer

Bone

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

The E2CAR trial is a single arm intervention trial. Eligible participants' autologous T-cells will be collected via leukapheresis then the T cells will be genetically modified in an on-site clean room laboratory to express a Chimeric Antigen Receptor (CAR) targeting the tumour associated antigen, EphA2. These modified T cells (the intervention) are called EphA2CAR T cells (GENERIC), Approximately 14-21 days following leukapheresis, participants will receive lymphodepletion chemotherapy, then 7 days later, a single intravenous infusion of autologous EphA2CAR T cells between 1 x 10e5 EphA2CAR T cells/kg and 1 x 10e7 EphA2CAR T cells/kg according to dose escalation trial design and subject to a maximum 50kg body weight. Target cell dose and dose escalations/de-escalations will be determined by a Clinical Committee using the ‘3+3’ trial design. Cohorts of 3 to 6 participants will be treated at each dose level to determine the maximum tolerated or maximum administered dose. Dose escalation for a new cohort will proceed if fewer than 33% of 3 or 6 subjects in the previous cohort experienced a dose limiting toxicity at their dose level. Data from both osteosarcoma and Ewing sarcoma patients will be combined when determining primary and secondary outcomes.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Treatment: Other

Description of the comparator or control

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

To determine the safety of administering EphA2 CAR T cells to patients with relapsed or refractory EphA2 positive osteosarcoma or Ewing sarcoma, or osteosarcoma undergoing first-line therapy where disease location precludes surgical resection of the primary tumour, using a dose escalation strategy: (a) based on the occurrence of all adverse events graded according to CTCAE v5.0.

Timepoint [1]

Within 3 months following EphA2 CAR T cell infusion.

Primary outcome [2]

To determine the safety of administering EphA2 CAR T cells to patients with relapsed or refractory EphA2 positive osteosarcoma or Ewing sarcoma, or osteosarcoma undergoing first-line therapy where disease location precludes surgical resection of the primary tumour, using a dose escalation strategy: (b) based on the occurrence of Cytokine Release Syndrome (CRS) graded according to ASTCT Consensus Grading tool

Timepoint [2]

Within 3 months following EphA2 CAR T cell infusion.

Primary outcome [3]

To determine the safety of administering EphA2 CAR T cells to patients with relapsed or refractory EphA2 positive osteosarcoma or Ewing sarcoma, or osteosarcoma undergoing first-line therapy where disease location precludes surgical resection of the primary tumour, using a dose escalation strategy: (c) based on the occurrence of Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) graded according to ASTCT Consensus Grading tool

Timepoint [3]

Within 3 months following EphA2 CAR T cell infusion.

Secondary outcome [1]

To determine the feasibility of manufacturing EphA2 CAR-T cells from paediatric patients with relapsed or refractory EphA2 positive osteosarcoma or Ewing sarcoma, or osteosarcoma undergoing first-line therapy where disease location precludes surgical resection of the primary tumour, to meet defined acceptance criteria and cell dose according to: a) successful manufacture of EphA2 CAR T cell products meeting pre-agreed acceptance criteria and target dose from apheresed T cell products.

Timepoint [1]

At least 7 days prior to CAR T cell infusion.

Secondary outcome [2]

To determine the feasibility of manufacturing EphA2 CAR T cells from paediatric patients with relapsed or refractory EphA2 positive osteosarcoma or Ewing sarcoma, or osteosarcoma undergoing first-line therapy where disease location precludes surgical resection of the primary tumour, to meet defined acceptance criteria and cell dose according to: b) Administration of at least one dose of EphA2 CAR T cells.

Timepoint [2]

At CAR T cell infusion.

Secondary outcome [3]

To determine the maximum tolerated dose of EphA2 CAR T cells when administered intravenously.

Timepoint [3]

Up to 28 days following EphA2 CAR-T cell infusion.

Secondary outcome [4]

To assess the functional capacity of EphA2 CAR-T cells generated from patients with solid tumours to target EphA2 expressing tumours in patients according to: (a) The degree of CAR T-cell expansion following infusion.

Timepoint [4]

Daily up to 28 days, weekly up to 12 weeks, then monthly up to 24 months following EphA2 CAR-T cell infusion

Secondary outcome [5]

To assess the functional capacity of EphA2 CAR-T cells generated from patients with solid tumours to target EphA2 expressing tumours in patients according to: (b) CAR T cell persistence or longevity following infusion.

Timepoint [5]

Daily up to 28 days, weekly up to 12 weeks, then monthly up to 24 months following EphA2 CAR-T cell infusion.

Secondary outcome [6]

To assess the functional capacity of EphA2 CAR-T cells generated from patients with solid tumours to target EphA2 expressing tumours in patients according to: (c) CAR-T cell population phenotype following infusion.

Timepoint [6]

Weekly up to 12 weeks, then monthly up to 12 months, then 6-monthly up to 24 months, then yearly up to 15 years following EphA2 CAR-T cell infusion.

Secondary outcome [7]

To assess the functional capacity of EphA2 CAR-T cells generated from patients with solid tumours to target EphA2 expressing tumours in patients according to: (d) CAR-T cell population clonality following infusion.

Timepoint [7]

Weekly up to 12 weeks, then monthly up to 12 months, then 6-monthly up to 24 months, then yearly up to 15 years following EphA2 CAR-T cell infusion.

Secondary outcome [8]

To assess the functional capacity of EphA2 CAR-T cells generated from patients with solid tumours to target EphA2 expressing tumours in patients according to: (d) evidence for CAR-T cell trafficking to tumours as assessed using histological tumour.

Timepoint [8]

Any time between 28 days and 24 months post E2CAR infusion.

Secondary outcome [9]

To assess the functional capacity of EphA2 CAR-T cells generated from patients with solid tumours to target EphA2 expressing tumours in patients according to: (e) the extent to which EphA2 antigen continues to be expressed on recurrent tumours following EphA2 targeted CAR T cell administration.

Timepoint [9]

Any time between 28 days and 24 months post E2CAR infusion.

Secondary outcome [10]

To assess the cytokine profile of patients after intravenous administration of EphA2 CAR-T cells

Timepoint [10]

Daily up to 4-8 weeks following EphA2 CAR-T cell infusion,

Secondary outcome [11]

To evaluate the clinical anti-tumour efficacy of EphA2 CAR-T cell therapy to determine: (a) achievement of complete response at clinical and/or imaging disease reassessment 28 and 90 days after administration of EphA2 CAR T cells.

Timepoint [11]

At 28 and 90 days after administration of EphA2 CAR T cells.

Secondary outcome [12]

To evaluate the clinical anti-tumour efficacy of EphA2 CAR-T cell therapy: (a) achievement of partial response at clinical and/or imaging disease reassessment 28 and 90 days after administration of EphA2 CAR T cells.

Timepoint [12]

At 28 and 90 days after administration of EphA2 CAR cells.

Secondary outcome [13]

To evaluate the clinical anti-tumour efficacy of EphA2 CAR-T cell therapy: (c) stable disease at clinical and/or imaging disease reassessment 28 and 90 days after administration of EphA2 CAR cells.

Timepoint [13]

At 28 and 90 days after administration of EphA2 CAR cells.

Secondary outcome [14]

To evaluate the clinical anti-tumour efficacy of EphA2 CAR-T cell therapy: (d) Progressive disease at clinical and/or imaging disease reassessment 28 and 90 days after administration of EphA2 CAR T cells.

Timepoint [14]

At 28 and 90 days after administration of EphA2 CAR cells.

Secondary outcome [15]

To evaluate the clinical anti-tumour efficacy of EphA2 CAR-T cell therapy: (e) best overall response for trial participants at clinical and/or imaging disease reassessment over the trial period.

Timepoint [15]

At 28 and 90 days after administration of EphA2 CAR cells.

Secondary outcome [16]

To evaluate the clinical anti-tumour efficacy of EphA2 CAR-T cell therapy to determine: (f) progression-free survival at clinical and/or imaging disease reassessment at 3, 6, 12 and 24 months after administration of EphA2 CAR T cells.

Timepoint [16]

At 3, 6, 12 and 24 months after administration of EphA2 CAR T cells.

Secondary outcome [17]

To evaluate the clinical anti-tumour efficacy of EphA2 CAR-T cell therapy: (g) measurement of circulating tumour DNA isolated from plasma (liquid biopsy).

Timepoint [17]

At 3, 6, 12 and 24 months after administration of EphA2 CAR T cells.

Secondary outcome [18]

To evaluate the clinical anti-tumour efficacy of EphA2 CAR-T cell therapy: (h) measurement of circulating CAR DNA isolated from plasma (liquid biopsy).

Timepoint [18]

At 3, 6, 12 and 24 months after administration of EphA2 CAR T cells.

Eligibility

Key inclusion criteria

Eligibility will be evaluated first by screening the tumour to determine EphA2-positivity (Stage 1). Participants with EphA2-positive tumours will then be assessed again to confirm eligibility for T-cell collection (apheresis) and manufacture of EphA2 CAR-T cell product (Stage 2), lymphodepletion and administration of CAR-T cells (Stage 3).

STAGE 1 (SCREENING)
* Age less than or equal to 21 years
* Documentation of high-risk osteosarcoma or Ewing sarcoma either through review of medical record, or in correspondence from a referring oncologist.
* Available tissue for tumour analysis of EphA2 expression, either archival, or planned biopsy
* Written informed consent for screening

STAGE 2 (APHERESIS AND CAR-T CELL MANUFACTURE)
* Confirmed EphA2-positive Ewing sarcoma or osteosarcoma (from STAGE 1, above)
* Relapsed or refractory disease after standard of care treatment or osteosarcoma undergoing first-line therapy where disease location precludes surgical resection of the primary tumour
o for which standard curative measures do not exist or are no longer effective
o evaluable for anatomic and/or metabolic response using cross sectional and/or PET scan imaging
* Lansky or Karnofsky score greater than or equal to 50 percent
* Estimated life expectancy of greater than or equal to 12 weeks
* Recovered from acute toxicities of prior therapy
* Adequate cardiac, renal, respiratory, liver and haematological function
* Using an acceptable form of contraception (female or male)
* Written informed consent for apheresis, CAR-T cell manufacture, lymphodepletion, and CAR-T cell infusion

STAGE 3 (LYMPHODEPLETION/CAR-T CELL INFUSION) ELIGIBILITY
* EphA2-positive Ewing sarcoma or osteosarcoma evaluable for anatomic and/or metabolic response using cross sectional or PET scan imaging
* Previously enrolled on the apheresis and manufacture STAGE of this trial with availability of an EphA2 CAR-T cell product meeting release criteria
* Estimated life expectancy of greater than or equal to 8 weeks
* Lansky or Karnofsky score greater than or equal to 50 percent
* Recovered from acute toxicities of prior therapy
* Adequate cardiac, renal, respiratory, liver and haematological function
* Using an acceptable form of contraception (female or male)

Minimum age

0 Years

Maximum age

21 Years

Sex

Both males and females

Healthy volunteers

Key exclusion criteria

STAGE 1 (SCREENING)
*Pregnancy or currently breast feeding
*Any major co-morbidity which would preclude subsequent participation in STAGEs 2 and 3

STAGE 2 (APHERESIS AND CAR-T CELL MANUFACTURE)
* Active hepatitis B or hepatitis C,
* HIV infection
* Uncontrolled active infection
* Primary or acquired immunodeficiency disorder
* Concurrent use of systemic steroids or immunosuppression at the time of apheresis, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during apheresis (steroids for disease treatment at times other than apheresis, and/or use of physiologic replacement hydrocortisone or inhaled steroids, are permitted)
* CNS metastases, including parenchymal or leptomeningeal involvement
* Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity
* Received any live vaccines within 30 days prior to apheresis

STAGE 3 (LYMPHODEPLETION/CAR-T CELL INFUSION) ELIGIBILITY
* Uncontrolled active infection.
* CNS metastases, including parenchymal or leptomeningeal involvement.
* Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity.
* Concurrent use of systemic steroids or immunosuppression at the time of cell infusion (steroids for disease treatment at times other than apheresis or cell infusion, and/or use of physiologic replacement hydrocortisone or inhaled steroids, are permitted).

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)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Phase 1

Type of endpoint/s

Safety

Statistical methods / analysis

Participants enrolled on Stages 2/3 of this trial will be included in the primary analysis population. Participants who are administered EphA2 CAR-T cells (STAGE 3) will be included in the safety and efficacy analyses.

As a Phase I trial, the primary focus will be on safety and feasibility of the EphA2 CAR-T cell approach. Data will be analysed using descriptive statistics.
To address the feasibility of this approach, the proportion of manufactured apheresis products meeting acceptance criteria and minimum cell dose will be determined.
To address safety, adverse events will be documented, dose-limiting toxicities and maximum tolerated dose will be described.

To address the exploratory objective of anti-tumour efficacy, the rates of complete and partial response, stable disease, progressive disease, progression-free survival and overall survival will be documented. Data related to expansion and persistence of CAR-T cells, circulating tumour and CAR DNA and participant cytokine profiles will also be described.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

12/01/2027

Actual

Date of last participant enrolment

Anticipated

24/11/2029

Actual

Date of last data collection

Anticipated

24/01/2032

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

The Children's Hospital at Westmead - Westmead

Recruitment postcode(s) [1]

2145 - Westmead

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Australian Government Department of Health, Disability and Ageing - Medical Research Futures Fund

Address [1]

Country [1]

Australia

Primary sponsor type

Government body

Name

Sydney Children's Hospitals Network

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Children's Hospitals Network Human Research Ethics Committee

Ethics committee address [1]

http://www.schn.health.nsw.gov.au/health-professionals/our-research/ethics-research-governance

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

23/06/2025

Approval date [1]

31/10/2025

Ethics approval number [1]

2024/ETH01141

Summary

Brief summary

EphA2 Chimeric Antigen Receptor (CAR) T cell Therapy for Children with Bone Tumours: A Phase I Clinical Trial

Brief description of the study purpose:
This study aims to assess the safety and feasibility of EphA2 CAR-T cell treatment for osteosarcoma and Ewing sarcoma in children where the sarcomas have either not responded to (refractory) or returned after (recurrent) standard treatment and no longer responding to standard treatment and no alternative treatment option exists, or the location of osteosarcoma prevents first time standard treatment. CAR T-cell therapy (Chimeric Antigen Receptor T-cell therapy) is a type of immunotherapy that uses a patient’s own genetically modified immune cells (T-cells) to fight certain cancers.

Who is it for:
Stage 1: You may be eligible for Stage 1 of this study if you are male or female age less than or equal to 21 years, with documented refractory or recurrent Ewing sarcoma or osteosarcoma no longer responding to standard treatment and no alternative treatment option exists, or osteosarcoma where disease location precludes standard first line treatment and you have enough previously collected tumour previously to testing for the EphA2 protein on your tumour cells. 
Stages 2 & 3: You may be eligible for Stages 2 & 3 if you have EphA2 protein on your tumour cells, measurable MRI, CT or PET scans, a life expectancy of at least 12 weeks (at least 8 weeks at Stage 3), sufficient heart, kidney, lung, liver and blood function, you have recovered from acute toxicities caused by any previous treatments, and your immune (T) cells have been successfully collected and made into EphA2 CAR-T cells.

Study Details:
Eligible participant's own immune (T) cells will be collected by filtering the participant's blood (leukapheresis) then genetically modified in a laboratory to a Chimeric Antigen Receptor (CAR) targeting the tumour associated antigen, EphA2.
Approximately 14-21 days following leukapheresis, participants will receive lymphodepletion chemotherapy, then 7 days later, a single intravenous infusion of autologous EphA2 CAR T cells according to dose escalation trial design and subject to a maximum 50kg body weight. Cohorts of 3 to 6 participants will be treated at a dose level to determine the maximum tolerated or maximum administered dose.

CAR T cell manufacturing feasibility will be determined by whether the manufactured CAR T cells meet quality acceptance criteria. CAR T cell safety will be determined by adverse events occurring after CAR T cell infusion. After CAR T cell infusion, follow-up assessments will include participant clinical assessment, including blood assays to determine anti-tumour efficacy, and to determine the rates of disease response, disease progression, and survival.

It is hoped this study will improve treatment outcomes for these patients with otherwise limited treatment options, and increase knowledge of CAR T cell treatment of solid tumours.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Caroline Bateman

Address

The Children's Hospital at Westmead (Corner Hawkesbury Road and, Hainsworth St, Westmead NSW 2145)

Country

Australia

Phone

+61 417404494

Fax

[email protected]

Contact person for public queries

Name

Caroline Bateman

Address

The Children's Hospital at Westmead (Corner Hawkesbury Road and, Hainsworth St, Westmead NSW 2145)

Country

Australia

Phone

+61 417404494

Fax

[email protected]

Contact person for scientific queries

Name

Dr Kavitha Gowrishankar

Address

The Children's Hospital at Westmead (Corner Hawkesbury Road and, Hainsworth St, Westmead NSW 2145)

Country

Australia

Phone

+61 414944648

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

No
No IPD sharing reason/comment: Contrary to SCHN policies and procedures

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.

Trial Review

Documents added manually

Documents added automatically