LeiomyosarcomaPhase 2DiTuSarcNCT05080790
Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Leiomyosarcoma
A Phase 2 study testing Dinutuximab Beta, Zoledronic acid, Interleukin-2 in people with Leiomyosarcoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 2 sites in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Leiomyosarcoma
- What is being tested?
- Dinutuximab Beta, Zoledronic acid, Interleukin-2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesGermany
- Study dates
- 15 Nov 2021to 20 Jan 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed leiomyosarcoma.
- ≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy (anthracycline-containing regimen).
- Patients must have a cryopreserved and formalin-fixed paraffin-embedded tumor sample available for submission to central pathology review.
- Signed Written Informed Consent.
- Men and women aged ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Show all 22Show fewer
- Measurable disease.
- Locally advanced/unresectable or metastatic disease.
- No prior therapy with any agent targeting GD2.
- Confirmed GD2-Expression proven on cryopreserved tissue tumor samples. A staining score of 2 on cryopreserved tissue is sufficient for enrollment of the patient.
- No treatment with biologic therapy, immunotherapy, chemotherapy, investigational agent for malignancy, or radiation ≤ 21 days before study registration.
- No participation in another clinical trial in the period 30 days prior to start of first dose.
- Patients should have resolution of any toxic effects of prior therapy (except alopecia) to NCI CTCAE, version 5.0, grade 1 or less.
- Not pregnant and not nursing; for women of childbearing potential who are sexually active, a negative pregnancy test (urinary or serum beta-HCG) done ≤ 7 days prior to treatment start is required.
- Absolute neutrophil count (ANC) ≥ 1,000/mm3.
- Platelet count ≥ 70,000/mm3.
- Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance > 45 mL/min.
- Total bilirubin ≤ 1,5 x upper limit of normal (ULN). If total bilirubin is greater than 1,5 x ULN, measure indirect bilirubin to evaluate for Gilbert's syndrome (if direct bilirubin is within normal range, participant may be eligible).
- AST/ALT ≤ 2.5 x upper limit of normal (ULN).
- Adequate pulmonary function (FEV1 > 2 liters or ≥ 75% of predicted for height and age).
- No clinical significant heart failure (NYHA<III) or ejection fraction (echocardiography or scintigraphy; EF > 40%)
- Female participants must be postmenopausal (no spontaneous menses for at least 2 years), surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent (at the discretion of the investigator), or if sexually active, have agreed to use an highly effective contraceptive method for the duration of their study participation (see Appendix 3 for guidance); patients should maintain adequate contraception for a minimum of 2 months after the last dose of dinutuximab beta. Male participants must agree to use an adequate contraception method as deemed appropriate by the investigator (e.g., vasectomy, double-barrier, partner using effective contraception) and to not donate sperm for a minimum of 5 months after treatment discontinuation.
Who cannot join
- Symptomatic, untreated, or uncontrolled brain metastases present.
- Patients with a known history of hypersensitivity to interleukin-2.
- Patients with a hypersensitivity to zoledronic acid or to other bisphosphonates.
- Need for invasive dental procedures. Preventive dental exams should be performed before starting zoledronic acid.
- Patients after allogenic stem cell transplantation or other allogenic organ transplantation (e.g., liver, kidney etc.).
- Patients with different malignant diseases other than sarcoma (measurable manifestations in the last 12 months or active therapy against the other malignant disease in the last 12 months).
Show all 13Show fewer
- Known active pulmonary disease with hypoxia defined as:
- Oxygen saturation < 85% on room air or
- Oxygen saturation < 88% despite supplemental oxygen.
- Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, ongoing active infection, or psychiatric illness/social situation that may potentially impair the participant's compliance with study procedures.
- Patients who have received prior anti-GD2 therapy, including chimeric antigen receptor (CAR) T cells directed against GD2 antigen.
- Lactating females are not eligible unless they have agreed not to breastfeed their infants.
- Any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
HELIOS Klinikum Bad Saarow
Bad Saarow, 15526
Helios Klinikum Berlin-Buch
Berlin, 13125
About this study
Official title: Combined Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Metastatic or Inoperable Leiomyosarcoma - DiTuSarc Study
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].
Read the detailed 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].
- Conditions
- Leiomyosarcoma
- Being tested
- Dinutuximab Beta, Zoledronic acid, Interleukin-2
- Medical subject headings
- Leiomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dinutuximab Beta, Zoledronic acid, Interleukin-2Drug
Five 5-week cycles (Q5W) of dinutuximab beta, zoledronic acid and low-dose interleukin (IL-2)
| Study group | Role | What they receive |
|---|---|---|
| 5 cycles (Q5W) of dinutuximab beta, interleukin-2 and zoledronic acid | Experimental | 5 cycles (Q5W) of dinutuximab beta, 20mg/m2/day, interleukin-2, 5.4x10^6, and zoledronic acid, 4 mg Receives: Drug: Dinutuximab Beta, Zoledronic acid, Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary objective of this study is to assess the feasibility of the combined treatment with dinutuximab beta, zoledronic acid and low-dose interleukin 2.
Feasibility rate, defined as the number of patients still on treatment and progression-free at Cycle 4 Day 5 divided by the number of all treated subjects.
Measured: 3 years, at EOS
Secondary outcomes (4)
A secondary objective of this study is to assess the safety and tolerability of the combined treatment with dinutuximab beta, zoledronic acid and low-dose interleukin 2.
To assess the safety and tolerability of the combined treatment of dinutuximab beta, zoledronic acid and low-dose interleukin-2 in patients with leiomyosarcomas, all adverse events will be assessed, and any alteration to the protocol in relation to study treatment will be assessed (e.g. discontinuation, reduction or delay of the treatment including the reasons for alterations of the predefined study treatment schedule).
Measured: 3 years, at EOS
An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.
Progression-free Survival (PFS) and Progression-free Survival after 6 months (PFSR6)
Measured: 3 years, at EOS
An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.
Masurement of Overall Response Rate (ORR).
Measured: 3 years, at EOS
An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.
Measurement of Overall Survival (OS).
Measured: 3 years, at EOS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2021
- Study start15 Nov 2021
- Primary completion20 Jan 2025
- Study completion20 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeiomyosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
- Sponsor type
- University, hospital or other
- Collaborators
- RECORDATI GROUP
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05080790
- Sponsor's protocol ID
- DiTuSarc / GISG-20
- Acronym
- DiTuSarc
- Status last verified
- Aug 2025
- First submitted
- 15 Jul 2021
- Last updated
- 17 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Treatment With Dinutuximab Beta, Zoledronic Acid and Low-dose Interleukin (IL-2) in Patients With Metastatic or Inoperable Leiomyosarcoma - DiTuSarc Study
- ClinicalTrials.gov ID
- NCT05080790
- Acronym / sponsor ID
- DiTuSarc / DiTuSarc / GISG-20
- Conditions
- Leiomyosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus NordwestUniversity, hospital or other
- Collaborators
- RECORDATI GROUP
- Study start
- 15 Nov 2021 (actual)
- Primary completion
- 20 Jan 2025 (actual)
- Study completion
- 20 Jan 2025 (actual)
- First posted
- 18 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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].
Detailed 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5 cycles (Q5W) of dinutuximab beta, interleukin-2 and zoledronic acid | Experimental | Drug: Dinutuximab Beta, Zoledronic acid, Interleukin-25 cycles (Q5W) of dinutuximab beta, 20mg/m2/day, interleukin-2, 5.4x10^6, and zoledronic acid, 4 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients must have histologically confirmed leiomyosarcoma.
- ≥ 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy (anthracycline-containing regimen).
- Patients must have a cryopreserved and formalin-fixed paraffin-embedded tumor sample available for submission to central pathology review.
- Signed Written Informed Consent.
- Men and women aged ≥ 18 years.
Key exclusion criteria (13 listed)
- Symptomatic, untreated, or uncontrolled brain metastases present.
- Patients with a known history of hypersensitivity to interleukin-2.
- Patients with a hypersensitivity to zoledronic acid or to other bisphosphonates.
- Need for invasive dental procedures. Preventive dental exams should be performed before starting zoledronic acid.
- Patients after allogenic stem cell transplantation or other allogenic organ transplantation (e.g., liver, kidney etc.).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dinutuximab Beta, Zoledronic acid, Interleukin-2Five 5-week cycles (Q5W) of dinutuximab beta, zoledronic acid and low-dose interleukin (IL-2) | Drug | 5 cycles (Q5W) of dinutuximab beta, interleukin-2 and zoledronic acid |
Primary outcome
The primary objective of this study is to assess the feasibility of the combined treatment with dinutuximab beta, zoledronic acid and low-dose interleukin 2.
Time frame: 3 years, at EOS
Feasibility rate, defined as the number of patients still on treatment and progression-free at Cycle 4 Day 5 divided by the number of all treated subjects.
4 secondary outcomes
A secondary objective of this study is to assess the safety and tolerability of the combined treatment with dinutuximab beta, zoledronic acid and low-dose interleukin 2.
Time frame: 3 years, at EOS
An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.
Time frame: 3 years, at EOS
An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.
Time frame: 3 years, at EOS
An additional secondary objective of this study is to assess the efficacy of the combined treatment with dinutuaseximab beta, zoledronic acid and low-dose interleukin 2.
Time frame: 3 years, at EOS
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2025.
- Individual participant dataSharing planned: No
Related trials for Leiomyosarcoma
RecruitingPhase 1
Testing Low-Dose Common Chemotherapy (Liposomal Doxorubicin) in Combination With an Anti-Cancer Drug, Peposertib, in Advanced Sarcoma
Metastatic Dedifferentiated Liposarcoma, Metastatic Leiomyosarcoma
Active, not recruitingPhase 2
Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma
Metastatic Leiomyosarcoma, Metastatic Soft Tissue Sarcoma
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Active, not recruitingPhase 1
A Phase I Trial of Combination Gemcitabine and Nab-Sirolimus in Advanced Leiomyosarcomas or Advanced Soft-Tissue Sarcomas With TSC2 or TSC1 Loss-of-function Mutations or Deletions
Leiomyosarcoma, Soft-tissue Sarcomas
RecruitingPhase 2
A Study of Ivonescimab in People With Leiomyosarcoma
Leiomyosarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dinutuximab Beta, Zoledronic acid, Interleukin-2 in people with Leiomyosarcoma, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary objective of this study is to assess the feasibility of the combined treatment with dinutuximab beta, zoledronic acid and low-dose interleukin 2. (time frame: 3 years, at EOS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.