International Phase I Trial of Dinutuximab Beta With VDC/IE in GD2-Positive Ewing Sarkoma

NCT06839703 | Not Yet Recruiting Phase 1

• 1 other identifier: CESS-GD2
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of the study is to investigate the feasibility, toxicity, and biological activity of the treatment with dinutuximab beta in combination with standard chemotherapy in EWS to give high-risk patients with a GD2 positiv pumor a benefit in treatment. Within the study is tested with three different dosages in a 3+3 design with three pre-defined dose levels.

Conditions

High-risk GD2-Positive Ewing Sarcoma

Keywords

Biomarker; GD2 expression; targeted therapy; high-risk Ewing Sarcoma

Outcome Measures

Primary Outcomes (1)

• GD2 Positivity

  local assessment for GD2 positivity

  after initial diagnosis and before study enrolment

Study Arms (1)

dinutuximab beta added to standard chemotherapy

EXPERIMENTAL

Dinutuximab beta is added in different dosages to the standard chemotherapy

Drug: Dinutuximab beta

Interventions

Dinutuximab beta DRUG

Dinutuximab beta is added in different dosages to the standard chemotherapy

dinutuximab beta added to standard chemotherapy

Eligibility Criteria

• Age: 12 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, newly diagnosed Ewing Sarcoma (m/f/d) or so-called Ewing-like sarcoma (i.e. translocation-positive small blue round cell sarcoma other than Rhabdomyosarcoma) of bone and / or soft tissue with evidence of EWS translocation by fluorescence in situ hybridization (FISH), real-time polymerase chain reaction (RT-PCR), or next-generation sequencing (NGS) assay
• High risk stratification (metastatic disease)
• Centrally confirmed GD2-positive tumor (biopsy of original and/or residual tumor or liquid biopsy in peripheral blood)
• Availability of fresh frozen tumor tissue for central GD2-detection
• Age ≥12 months
• Start of first line treatment according to standard induction treatment (Cycle 1-4: VDC - IE - VDC - IE)
• Wash-out phase with a minimum of 14 days after the last the dose of the last chemotherapy
• Lansky (\<16 years) Performance Score ≥70% or ECOG (≥16 years) ≤ 2
• Adequate bone marrow function as evidenced by meeting all the following requirements:
• White blood cell count \> 2000/μl
• ANC ≥1000 cells/μL (G-CSF allowed)
• Platelet count 75,000 cells/μL without the use of platelet transfusion within the last 2 days
• Hemoglobin ≥9 g/dL without the use of red blood cell transfusion within the last 2 days
• Adequate hepatic function as evidenced by meeting all the following requirements:
• Serum total bilirubin ≤1.5 x upper limit of normal (ULN)

You may not qualify if:

• Relapsed or refractory Disease state
• Patients with hypersensitivity against at least 1 component of the investigational medicinal product
• Significant illnesses and/or any of the following:
• significant psychiatric disabilities or uncontrolled seizure disorders
• active uncontrolled peptic ulcer disease
• clinically significant neurologic deficit or objective peripheral neuropathy
• clinically significant, symptomatic fluid in a third space
• Active and uncontrolled CNS metastases (indicated by clinical symptoms, cerebral edema, corticosteroid and/or anticonvulsant requirement, or progressive disease); for controlled CNS metastases, patient should have been off corticosteroids for at least 28 days without overt evidence of significant neurological deficits prior to enrollment
• Significant cardiac conduction abnormalities, including known familial prolonged QT syndrome, or screening QTc \>480 msec
• Active, uncontrolled infection or an unexplained fever \>38.5°C which in the Investigator's opinion might compromise the patient's participation in the study or affect the study outcome
• Chronic Grade ≥2 diarrhea
• Diagnosis of any malignancy other than the disease under study
• Any other medical or social condition deemed by the Investigator to be likely to interfere with a patient's ability to cooperate and participate in the study or interfere with the interpretation of the results.

Sponsors & Collaborators

• Prof. Dr. Dirk Reinhardt: lead

MeSH Terms

Interventions

dinutuximab

Central Study Contacts

Helena Kerp, PhD

CONTACT

+49 201 74 94 96 0; cess-gd2@gpoh-trials.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Por. Dr. Dirk Reinhardt

Model Details: This is a multi-center, phase 1, open-label, dose escalation study enrolling high-risk Ewing sarcoma patients that have been tested with GD2-positivity in a classical 3+3 design.

Study Record Dates

• First Submitted: February 17, 2025
• First Posted: February 21, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share