Seclidemstat + Chemotherapy for Ewing Sarcoma

Not currently recruiting at 17 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for certain sarcomas, including Ewing sarcoma and myxoid liposarcoma. Researchers aim to determine the effectiveness of seclidemstat, an experimental treatment, both alone and combined with chemotherapy drugs cyclophosphamide and topotecan, in treating these cancers. It targets individuals whose sarcomas have returned or not responded to previous treatments. Suitable candidates have a confirmed diagnosis of Ewing sarcoma or similar sarcomas and have undergone at least one prior treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that seclidemstat is generally safe, with most patients tolerating it well. However, a serious and unexpected side effect led to a temporary pause in some studies. The FDA later permitted these studies to resume.

Researchers are also evaluating the safety and tolerability of seclidemstat when combined with cyclophosphamide and topotecan. Current evidence suggests it is generally safe, but more data is needed for confirmation.

Overall, while early studies appear promising, it is important to understand that this treatment remains in the early stages of testing. Researchers continue to learn about its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using seclidemstat in combination with chemotherapy for Ewing sarcoma because it works differently from the standard treatments like vincristine, doxorubicin, and cyclophosphamide. Seclidemstat is unique as it acts by inhibiting an enzyme involved in gene regulation, potentially preventing tumor growth at the genetic level. This new mechanism of action, combined with traditional chemotherapy agents like cyclophosphamide and topotecan, aims to enhance the overall effectiveness against these aggressive tumors. By targeting cancer more precisely, seclidemstat offers hope for improved outcomes and fewer side effects compared to conventional therapies.

What evidence suggests that this trial's treatments could be effective for Ewing sarcoma?

Studies have shown that seclidemstat can help shrink tumors in some patients with Ewing sarcoma. One study found that a patient's tumor decreased in size after just a few months of treatment. Seclidemstat works by reversing the effects of a fusion gene, which forms by joining parts of two different genes and is often involved in Ewing sarcoma. In this trial, one treatment arm combines seclidemstat with the chemotherapy drugs cyclophosphamide and topotecan, showing early positive results in patients who have already tried other treatments. This combination aims to enhance the overall effect against cancer cells. These findings suggest that seclidemstat, whether used alone or with chemotherapy, could be promising in treating Ewing sarcoma and related conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Damon Reed, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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

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 have had targeted radiation therapy recently.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.11514

Phase 1 trial of seclidemstat (SP-2577) in patients with ... One pt at 600 mg BID achieved a reduction in target lesions starting at end of C2 with further target lesion tumor shrinkage through end of C4 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40852926/

Seclidemstat (SP-2577) induces transcriptomic ... Treatment with the small molecule SP-2509 results in reversal of the transcriptional activity of the FET fusion that causes Ewing sarcoma, EWSR1 ...

3. investors.salariuspharma.com investors.salariuspharma.com/news-releases/news-release-details/clinical-data-salarius-pharmaceuticals-seclidemstat-patients-mds

Clinical Data on Salarius Pharmaceuticals' Seclidemstat in ... The median overall survival was 18.5 months (95% CI, range 6.1-30.9 months), median event-free survival was 7.2 months (95% CI, range 6.3-8.2 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03600649

Clinical Trial of SP-2577 (Seclidemstat) in Patients With ... To evaluate the safety and tolerability of seclidemstat (SP-2577) as a single agent and in combination with topotecan and cyclophosphamide in patients with ...

5. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/9/1584/764560/Seclidemstat-SP-2577-Induces-Transcriptomic

Seclidemstat (SP-2577) Induces Transcriptomic ... Treatment with the small molecule SP-2509 results in reversal of the transcriptional activity of the FET fusion that causes Ewing sarcoma, EWSR1::FLI1. A ...

6. targetedonc.com targetedonc.com/view/fda-enforces-partial-hold-on-trial-of-seclidemstat-in-mds-cmml

FDA Enforces Partial Hold on Trial of Seclidemstat in MDS ... Following the report of a serious and unexpected grade 4 adverse effect, a partial clinical hold has been placed on the phase 1 trial ...

7. investors.salariuspharma.com investors.salariuspharma.com/news-releases/news-release-details/salarius-completes-dose-escalation-stage-phase-12-clinical-trial

Salarius Completes Dose-Escalation Stage of Phase 1/2 ... Ewing-related sarcoma patients will continue to be treated with single-agent seclidemstat to generate more safety and early efficacy activity in this patient ...