Seclidemstat + Chemotherapy for Ewing Sarcoma

Recruiting at 15 trial locations

Overseen By Rebecca Griffith-Eskew

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Salarius Pharmaceuticals, LLC

Must not be taking: Antineoplastics, Immunotherapy, CYP inhibitors

Disqualifiers: HIV, Heart disease, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

50 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications, such as moderate or strong inhibitors or inducers of major CYP enzymes, at least 14 days before starting the trial. If you are on any of these medications, you will need to discuss with your doctor about stopping them before joining the trial.

What data supports the effectiveness of the drug combination of Seclidemstat, Cyclophosphamide, and Topotecan for treating Ewing Sarcoma?

Research shows that the combination of cyclophosphamide and topotecan has been used as a salvage therapy for relapsed Ewing sarcoma, with some patients experiencing stable disease or partial response. Additionally, camptothecin agents like topotecan have shown activity against Ewing sarcoma, especially when combined with other drugs. ^{1 2 3 4 5}

Is the combination of Seclidemstat, Cyclophosphamide, and Topotecan safe for treating Ewing Sarcoma?

The combination of Cyclophosphamide and Topotecan has been used in patients with Ewing Sarcoma, showing manageable side effects like temporary low blood cell counts and fever with low white blood cells. These treatments have been generally tolerable, but some patients needed blood transfusions or experienced fever. ^{1 2 3 6 7}

What makes the drug combination of Seclidemstat, Cyclophosphamide, and Topotecan unique for treating Ewing Sarcoma?

This treatment is unique because it combines Seclidemstat, a novel drug, with Cyclophosphamide and Topotecan, which have shown activity in relapsed Ewing Sarcoma. The addition of Seclidemstat, which may target specific cancer pathways, could enhance the effectiveness of the existing chemotherapy regimen. ^{1 2 3 8 9}

What is the purpose of this trial?

This trial tests seclidemstat alone and with other drugs in patients with specific types of sarcoma, especially those who haven't responded to other treatments. The treatment aims to block cancer growth and use chemotherapy to kill cancer cells.

Research Team

Damon Reed, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for patients aged 12 and older, weighing at least 40 kg, with specific sarcomas including Ewing or related types that are relapsed/refractory to prior treatments. Participants must have good performance status, adequate organ function, and a life expectancy over four months. They should not have had certain recent treatments or uncontrolled illnesses.

Inclusion Criteria

My blood tests show normal organ function and I haven't needed a blood transfusion in the last week.

I am mostly active and can care for myself regardless of my age.

I am at least 12 years old and weigh 40 kg or more.

Exclusion Criteria

I have had targeted radiation therapy recently.

Participation in a prior investigational study within 30 days prior to Cycle 1 Day 1 or within 5 half-lives of the investigational product

I haven't had any cancer treatments in the last 3 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive seclidemstat as a single agent or in combination with topotecan and cyclophosphamide

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

At least 4 weeks

Treatment Details

Interventions

• Cyclophosphamide
• Seclidemstat
• Topotecan

Trial Overview The trial tests Seclidemstat alone in select sarcoma patients and in combination with Topotecan and Cyclophosphamide for those with Ewing sarcoma. It's an open-label study where all participants receive the drugs without being compared to a placebo or other treatment.

Participant Groups

Group I: Sarcomas with FET-family translocations, including demoplastic small round cell tumors Experimental Treatment 1 Intervention

Twice-daily administration of oral seclidemstat

Group II: Myxoid Liposarcoma Experimental Treatment 1 Intervention

Twice-daily administration of oral seclidemstat

Group III: Ewing sarcoma, combination therapy Experimental Treatment 3 Interventions

Twice daily administration of seclidemstat in combination with cyclophosphamide and topotecan

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Salarius Pharmaceuticals, LLC

Lead Sponsor

Trials

5

Recruited

160+

National Pediatric Cancer Foundation

Collaborator

Trials

8

Recruited

300+

Findings from Research

In a study of 110 patients with metastatic Ewing sarcoma or primitive neuroectodermal tumor (PNET), the combination of topotecan and cyclophosphamide showed promising activity, with 21 out of 37 patients achieving partial responses.

Amifostine, intended as a cytoprotective agent, did not provide myeloprotection, and overall survival rates remained unchanged compared to previous studies, indicating that while some treatments showed activity, the prognosis for these patients remains poor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. Bernstein, ML., Devidas, M., Lafreniere, D., et al.[2013]

The combination of topotecan and cyclophosphamide (TC) was found to be tolerable in adults with recurrent sarcoma, but it showed only modest effectiveness, with a median time to progression of 2.5 months and limited partial responses in some patients.

Hematologic toxicity was a significant concern, with nearly half of the patients requiring blood transfusions and a third experiencing fever and neutropenia, highlighting the need for alternative treatment options for this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan and cyclophosphamide in adults with relapsed sarcoma. Blanchette, P., Hogg, D., Ferguson, P., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cyclophosphamide and topotecan as first-line salvage therapy in patients with relapsed ewing sarcoma at a single institution. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report. [2023]

3. Egypt pubmed.ncbi.nlm.nih.gov

Camptothecin-based regimens for treatment of ewing sarcoma: past studies and future directions. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Novel bone cancer drugs: investigational agents and control paradigms for primary bone sarcomas (Ewing's sarcoma and osteosarcoma). [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Ifosfamide plus etoposide in newly diagnosed Ewing's sarcoma of bone. [2022]

7. Egypt pubmed.ncbi.nlm.nih.gov

Topotecan and cyclophosphamide in adults with relapsed sarcoma. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Pilot Study of Adding Vincristine, Topotecan, and Cyclophosphamide to Interval-Compressed Chemotherapy in Newly Diagnosed Patients With Localized Ewing Sarcoma: A Report From the Children's Oncology Group. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Ewing Sarcoma: Current Management and Future Approaches Through Collaboration. [2022]