Trial Title:
To Evaluate the Efficacy and Safety of Naxitamab in Patients With Refractory Ewing's Sarcoma (Butterfly)
NCT ID:
NCT05968768
Condition:
Ewing Sarcoma
Conditions: Official terms:
Sarcoma
Sarcoma, Ewing
Conditions: Keywords:
Ewing Sarcoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Naxitamab
Description:
Naxitamab will be used only in a hospital setting and must be administered under the
supervision of a doctor with experience in the use of oncological therapies. The
medicinal product must be administered by a healthcare professional prepared to deal
appropriately with severe allergic reactions, including anaphylaxis, in an environment
that provides immediate, full access to resuscitation. The patient should have 2
well-functioning IV accesses before any naxitamab treatment is initiated. The solution
should be administered through a peripheral or central intravenous catheter. Other
concomitant intravenous medicinal products should be administered through separate
intravenous access. Before the start of each infusion, premedication will be carried out.
Arm group label:
Experimental - Naxitamab Arm
Other name:
danyelza
Summary:
Prospective, interventional, open, randomized, national, multicenter, non-commercial
trial
Detailed description:
The study includes:
1. Biology screening: to estimate expression on GD2 on Ewing sarcoma cells from tumor
tissue from archival material. Availability of tumor tissue is required for
pre-screening testing to determine GD2 expression. To be screened for potential
enrollment into the study patients or their legal representatives must have signed
the pre-screening informed consent form (ICF) to consent to using their archival
tumor sample to test the expression of GD2 in their tumor. The expression level of
GD2 will be characterized in tumor tissue by immunohistochemistry (IHC) at a local
and a central diagnostic testing laboratory.
2. Standard stratifying diagnostic tests (laboratory assessment: morphology, blood
chemistry including ALT, AST, eGFR, creatinine, sodium, potassium, coagulation,
urine analysis including pH, blood, protein, leukocytes, glucose, urobilinogen,
bilirubin, ketones, nitrites, specific gravity, vital signs (body temperature,
systolic and diastolic blood pressure, and pulse rate), ECG, cardiac function test,
imaging test: CT/MRI scan).
3. Patients with GD2 expression will be randomized in proportions (2:1) to the
experimental (D) and control groups (S). The cohort D will consist of 16 subjects,
the cohort S 8 subjects. The exploratory cohort D will receive the experimental
regimen in 3-week cycles consisting of irinotecan given intravenously (iv) 50 mg/m2
after oral temozolomide 100 mg/m2 on days 1-5 and naxitamab administered iv 2.25
mg/kg/day over 30 - 60 minutes, days 2, 4, 8 and 10 (up to 150 mg/day; total 9 mg/kg
per cycle), and GM-CSF 250 mg/m2/day subcutaneously, days 6-10. Patients randomized
to arm S will receive IT alone. Treatment cycles will be repeated every 21 days
summary to 6 cycles or until disease progression, or subsequent relapsed, or
occurrence of intolerable toxicity, or any event making impossible treatment
continuation, or investigator's judgment, or withdrawal of consent. All activities
are presented in Schedule of Assessments (SoA) at the end of the study synopsis.
4. Patients will be recalculated according to the intent to treat (ITT) rule.
5. The study will be conducted in accordance to GCP and after EC approval of the
protocol.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically proven Ewing sarcoma of the bone or soft tissues.
2. Subject's archival tumour sample (formalin-fixed, paraffin-embedded; 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 Clinical trial
protocol BUTTERFLY version 1.0 of 30.09.2022 r.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:
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 corrected QT interval (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 tri
Gender:
All
Minimum age:
2 Years
Maximum age:
21 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Mother and Child Institute
Address:
City:
Warsaw
Zip:
01-211
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Katarzyna Maleszewska
Phone:
+48 22 32 77 205
Email:
klinika.onkologii@imid.med.pl
Investigator:
Last name:
Anna Raciborska, Prof
Email:
Principal Investigator
Facility:
Name:
Wroclaw Medical University
Address:
City:
Wrocław
Zip:
50-556
Country:
Poland
Status:
Not yet recruiting
Contact:
Last name:
Anna Jodłowska-Kopacz
Phone:
48 71 733 27 92
Email:
badaniakliniczne@usk.wroc.pl
Investigator:
Last name:
Marek Ussowicz, Prof.
Email:
Principal Investigator
Start date:
October 24, 2023
Completion date:
July 31, 2028
Lead sponsor:
Agency:
Anna Raciborska
Agency class:
Other
Collaborator:
Agency:
Wroclaw Medical University
Agency class:
Other
Source:
Institute of Mother and Child, Warsaw, Poland
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05968768
