To evaluate the efficacy and safety of naxitamab in patients with refractory Ewing's sarcoma.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Instytut Matki I Dziecka

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Sep 2023 → ongoing

Decision date (initial)

2024-08-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Agencja Badań Medycznych

External identifiers

EU CT number

2024-514441-11-00

EudraCT number

2022-003812-98

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Pharmacokinetic, Efficacy

Safety assessment of the addition of naxitamab to standard 3-week chemotherapy (CHT) in patients with refractory Ewing's sarcoma (ES)

Secondary objectives 3

1. To assess the clinical benefit of naxitamab add-on to the standard backbone IT chemotherapy and to estimate efficacy parameters that can be used for planning future phase III studies.
2. This secondary objective has been redacted following transparency rules and protection of confidential information.
3. Ancillary studies – biology studies: to evaluate the expression of GD2 in Ewing sarcoma cells in refractory/relapsed Ewing sarcoma patients.

Conditions and MedDRA coding

Ewing's sarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically proven Ewing sarcoma of the bone or soft tissues.
2. Subject's archival tumour sample (formalin-fixed, paraffinembedded; FFPE) available for evaluation of GD2 expression.
3. Documented disease progression (during or after completion of at least one line treatment) or any subsequent recurrence.
4. GD2 positive tumor assessed by IHC.
5. Age ≥ 2 years and ≤ 21 years.
6. Life expectancy of at least 12 weeks from the time informed consent was signed.
7. Previous systemic anticancer treatment completed ≥ 3 weeks, major surgery ≥ 2 weeks, and radiation therapy ≥ 4 weeks prior to study enrollment.
8. Recovered from adverse effects of prior surgery, radiotherapy, or anti-neoplastic therapy at the discretion of the investigator.
9. Signing of informed consent for trial participation (including for naxitamab treatment) according with current legal regulations.
10. Consent to the use of effective contraception throughout the period of the study and a minimum of 1 year after discontinuation of study treatment in patients at puberty and sexual maturity.

Exclusion criteria 13

1. Failure to meet any of the inclusion criteria.
2. Not eligible to IT.
3. Previous treatment with an anti-GD2 antibody.
4. Hypersensitivity to the study drugs or any of their ingredients (covers IT and naxitamab).
5. Simultaneous treatment with other drugs which might interact with naxitamab or IT regimen.
6. Persistent toxicity related to prior therapy, making it impossible to treat with naxitamab.
7. Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTc >480 msec.
8. Symptoms of congestive heart failure or left ventricular ejection fraction <50%.
9. Inadequate pulmonary function defined as evidence of dyspnea at rest, exercise intolerance, and/or chronic oxygen requirement. In addition, room air pulse oximetry < 94% and/or abnormal pulmonary function tests if these assessments are clinically indicated.
10. Requirement, or likely requirement, for corticosteroids at doses >10 mg prednisolone (or equivalent) per day or other immunosuppressive agents.
11. Diagnosis of other malignancies before study inclusion.
12. Planning to become pregnant (while being treated with IT or naxitamab), pregnancy or breastfeeding.
13. Other acute or persistent disorders, behaviors or abnormal laboratory test results, which might increase the risk related to the participation in this clinical trial or to taking the study drug, or which might influence the interpretation of the study results, or which, in the investigator's opinion, disqualify a patient from participating in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Safety and tolerability will be assessed based on an analysis of adverse events on all enrolled subjects. These events will be divided according to severity, seriousness, affected organ or system and analyzed for:
2. number of serious adverse events (SAE)
3. the number of adverse events (AE), including events of particular importance to the incidence and severity of adverse events occurring during treatment (TEAE) (encoded according to the preferred term and class of organ systems using the Medical Dictionary for Regulatory Activities (MedDRA); these events will be estimated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)
4. the result of a medical examination with the analysis of recorded vital signs
5. assessment of laboratory abnormalities according to NCI CTCAE v5.0
6. This primary end point has been redacted following transparency rules and protection of confidential information.

Secondary endpoints 5

1. To assess the efficacy of the use of naxitamab in combination with standard IT chemotherapy versus chemotherapy alone:
2. EFS (Event-Free Survival) - from randomization to the date of disease progression, recurrence, second malignancy, death or to date of last follow-up for patients without events,
3. PFS (Progression-Free Survival) - from randomization to progression of the disease,
4. ORR (Overall Response Rate) - defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) according WHO criteria,
5. OS (Overall Survival) - from randomization to subject's death.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Instytut Matki I Dziecka

Sponsor organisation

Instytut Matki I Dziecka

Address

Ul Marcina Kasprzaka 17 A

City

Warsaw

Postcode

01-211

Country

Poland

Scientific contact point

Organisation

Instytut Matki I Dziecka

Contact name

Klinika Onkologii i Chirurgii Onkologicznej Dzieci i Młodzieży IMID

Public contact point

Organisation

Instytut Matki I Dziecka

Contact name

Klinika Onkologii i Chirurgii Onkologicznej Dzieci i Młodzieży IMID

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications