Clinical Trials Logo

Clinical Trial Summary

Dinutuximab beta was designed to bind to neuroblastoma cells and other cancer cells that express the GD2 antigen, such as STS/LMS cells, and it is believed that this binding "labels" the cells an makes them a better target. In addition, γδ T cells can safely be expanded in-vivo using intravenous zoledronic acid and subcutaneous interleukin-2 (IL-2) in patients with different types of solid tumors [Dieli et al., 2007; Pressey et al., 2016]. It is supposed that combination treatment using dinutuximab beta, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as GD2 expressing LMS both rational and feasible [Fisher et al., 2015].


Clinical Trial Description

Soft-tissue sarcomas (STS) are a heterogeneous group of malignancies characterized by both their relatively low incidence and their poor prognosis, encompassing more than 60 distinct diagnoses. Leiomyosarcoma (LMS), together with liposarcoma, is one of the most frequent sub-types amongst STS and accounts for up to 25% of all newly diagnosed STS [Guo et al., 2015]. The absence of definite causative risk factors for LMS, whether genetic, epigenetic or environmental, make this disease particularly difficult to understand and difficult to treat. Classically, soft-tissue sarcomas (STS) have been treated as a single disease and with LMS as one of the most frequent sub-types the results with conventional therapies have been rather disappointing, especially in the advanced setting. The use of novel therapeutic approach such immunotherapy has also not yielded the same success compared to other tumor entities, whereas the heterogeneity of this malignancy certainly plays a role. Current immunotherapy trials mostly use monoclonal antibodies to target those molecules or interactions, that essentially "take the brakes off" the immune system. If the underlying immune response however is poor, simply taking the brakes off will be insufficient. In tumors that do not trigger a sufficient immune response, it might be an advantages strategy to try make the tumor a better target and thus trigger a better antitumor immune response. Strategies that incorporate the tumoricidal properties of gammadelta T cells (γδ T cells) represent a promising immunotherapeutic strategy for treatment of solid malignancies including neuroblastoma (NB) [Dieli et al., 2007]. An evaluation of pooled data from 132 published in vitro experiments shows a consistent improvement in the cytotoxicity of γδ T cells in the presence of antitumor antibodies. Immunotherapy using γδ T cells alone shows promising clinical activity, but there is a strong preclinical rationale for combining this treatment modality with cancer-targeting antibodies to augment its efficacy [Fisher et al., 2014]. Dinutuximab beta was designed to bind to neuroblastoma cells and other cancer cells that express the GD2 antigen, such as STS/LMS cells, and it is believed that this binding "labels" the cells an makes them a better target. In addition, γδ T cells can safely be expanded in-vivo using intravenous zoledronic acid and subcutaneous interleukin-2 (IL-2) in patients with different types of solid tumors [Dieli et al., 2007; Pressey et al., 2016]. It is supposed that combination treatment using dinutuximab beta, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as GD2 expressing LMS both rational and feasible [Fisher et al., 2015]. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05080790
Study type Interventional
Source Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Contact Daniel Pink, Dr.
Phone 033631 73527
Email daniel.pink@helios-gesundheit.de
Status Recruiting
Phase Phase 2
Start date November 15, 2021
Completion date July 26, 2024

See also
  Status Clinical Trial Phase
Recruiting NCT04535271 - Metronomic Trabectedin, Gemcitabine, and Dacarbazine for Leiomyosarcoma Phase 2
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Recruiting NCT06088290 - Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Participants With Metastatic Leiomyosarcoma Phase 2/Phase 3
Withdrawn NCT04906876 - A Phase 2 Study of 9-ING-41Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas Phase 2
Terminated NCT02940041 - Concordance Between Sonography Amd MRI for Presurgical Diagnosis of Uterine Mesenchymal Malignant Tumors
Completed NCT01442662 - Efficacy of Gemcitabine With Pazopanib as Second Line Treatment in Patient With Metastatic or Relapsed Uterine Phase 2
Completed NCT00062868 - LMP-specific T-cells for Patients With Relapsed EBV-positive Lymphoma Phase 1
Recruiting NCT04214457 - Development of a Predictive Model for Early Differential Diagnosis of Uterine Leiomyomas and Leiomyosarcomas
Active, not recruiting NCT04420975 - Nivolumab and BO-112 Before Surgery for the Treatment of Resectable Soft Tissue Sarcoma Phase 1
Terminated NCT04099277 - A Study of LY3435151 in Participants With Solid Tumors Phase 1
Not yet recruiting NCT05548179 - Exploring Clinical Trial Experiences of People With Leiomyosarcoma
Recruiting NCT02983539 - Detection of Circulating Tumor Cells in Patients With Sarcomas
Completed NCT00093080 - Study of AP23573/MK-8669 (Ridaforolimus), A Mammalian Target of Rapamycin (mTOR) Inhibitor, in Participants With Advanced Sarcoma (MK-8669-018 AM1)(COMPLETED) Phase 2
Active, not recruiting NCT04624178 - A Study of Rucaparib and Nivolumab in People With Leiomyosarcoma Phase 2
Terminated NCT03959033 - Patient Reported Outcome Measures (PROMs) With Trabectedin
Recruiting NCT02275286 - Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients Phase 1/Phase 2
Active, not recruiting NCT01956084 - Cytotoxic T Cells to Treat Relapsed EBV-positive Lymphoma Phase 1
Completed NCT01426633 - Combination Therapy of Gemcitabine and Trabectedin in L-sarcomas Phase 1
Completed NCT00400569 - Phase II Study of Sunitinib Malate for Metastatic and/or Surgically Unresectable Soft Tissue Sarcoma Phase 2
Active, not recruiting NCT05269355 - A Study of Unesbulin in Participants With Advanced Leiomyosarcoma (LMS) Phase 2/Phase 3