Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas

Phase 1

Active, not recruiting

• Conditions: Ewing Sarcoma; Clear Cell Sarcoma; Myoepithelial Tumor; Desmoplastic Small Round Cell Tumor; Angiomatoid Fibrous Histiocytoma; Myxoid Liposarcoma; Sarcoma,Soft Tissue; Extraskeletal Myxoid Chondrosarcoma; Sclerosing Epithelioid Fibrosarcoma; Fibromyxoid Tumor
• Interventions: Drug: Seclidemstat; Drug: Cyclophosphamide; Drug: Topotecan

• Registration Number: NCT03600649
• Lead Sponsor: Salarius Pharmaceuticals, LLC

Brief Summary

Single agent, non-randomized, open label expansion in select sarcoma patients including myxoid liposarcoma and other sarcomas that share similar chromosomal translocations to Ewing sarcoma; AND dose expansion of the combination of seclidemstat with topotecan and cyclophosphamide in patients with Ewing sarcoma

Detailed Description

The single agent expansion cohort of select sarcoma patients will enroll myxoid liposarcoma patients and patients with other sarcomas that share similar chromosomal translocations to Ewing sarcoma (FET-family translocations), including but not limited to desmoplastic small round cell tumor.

A safety lead-in dose escalation and dose expansion will be conducted assessing the combination of seclidemstat with topotecan and cyclophosphamide in patients with relapsed or refractory Ewing sarcoma.

Study Timeline

• Study Start: 2018-06-04
• Study First Submitted: 2018-06-04
• Study First Submitted QC: 2018-07-19
• Study First Posted: 2018-07-26
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-20
• Last Update Posted: 2023-11-21
• Primary Completion: 2025-09
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ewing sarcoma, combination therapy	Topotecan	Twice daily administration of seclidemstat in combination with cyclophosphamide and topotecan
Ewing sarcoma, combination therapy	Cyclophosphamide	Twice daily administration of seclidemstat in combination with cyclophosphamide and topotecan
Myxoid Liposarcoma	Seclidemstat	Twice-daily administration of oral seclidemstat
Sarcomas with FET-family translocations, including demoplastic small round cell tumors	Seclidemstat	Twice-daily administration of oral seclidemstat
Ewing sarcoma, combination therapy	Seclidemstat	Twice daily administration of seclidemstat in combination with cyclophosphamide and topotecan

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of seclidemstat (SP-2577) as a single agent and in combination with topotecan and cyclophosphamide measured by dose limiting toxicities and adverse events according to CTCAE version 5.0	From screening through at least 30 days after end of treatment, up to approximately 24 months	To evaluate the safety and tolerability of seclidemstat (SP-2577) as a single agent and in combination with topotecan and cyclophosphamide in patients with relapsed or refractory Ewing sarcoma and select sarcomas. Toxicities will be graded in severity per the guidelines outlined in the NCI CTCAE version 5.0. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which ≥ 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity.

Secondary Outcome Measures

Name	Time	Method
Characterization of the pharmacokinetics of SP-2577 as measured by median half-life	From screening through at least 30 days after end of treatment, up to approximately 24 months	To characterize pharmacokinetics of seclidemstat as a single agent and in combination with topotecan and cyclophosphamide.
Food effects on the pharmacokinetics of SP-2577 as measured in both fasted and fed populations, primarily measured by apparent clearance.	From screening through at least 30 days after end of treatment, up to approximately 24 months	To evaluate the effect of food on the pharmacokinetics of seclidemstat. Both fasted and fed PK samples will be taken.
Determine the maximum tolerated dose of SP-2577 as determined by dose limiting toxicities measured according to CTCAE version 5.0	From screening through at least 30 days after end of treatment, up to approximately 24 months	To determine the maximum tolerated dose (MTD) of seclidemstat as a single agent and in combination with topotecan and cyclophosphamide in patients with relapsed or refractory Ewing sarcoma. Toxicities will be graded in severity per the guidelines outlined in the NCI CTCAE version 5.0. The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which ≥ 2 patients from a cohort of 3 to 6 patients experience a dose-limiting toxicity.
Characterization of the pharmacokinetics of SP-2577 as measured by peak plasma concentration	From screening through at least 30 days after end of treatment, up to approximately 24 months	To characterize pharmacokinetics of seclidemstat as a single agent and in combination with topotecan and cyclophosphamide.
Characterization of the pharmacokinetics of SP-2577 as measured by area under the curve	From screening through at least 30 days after end of treatment, up to approximately 24 months	To characterize pharmacokinetics of seclidemstat as a single agent and in combination with topotecan and cyclophosphamide.
Characterization of the pharmacokinetics of SP-2577 as measured by apparent clearance of seclidemstat	From screening through at least 30 days after end of treatment, up to approximately 24 months	To characterize pharmacokinetics of seclidemstat as a single agent and in combination with topotecan and cyclophosphamide.
Anti-tumor activity as measured according to RECIST 1.1 criteria based upon radiological assessments.	From screening through at least 30 days after end of treatment, up to approximately 24 months	To evaluate the anti-tumor activity of seclidemstat as a single agent and in combination with topotecan and cyclophosphamide. Tumor response will be measured according to RECIST 1.1 criteria. Radiological assessments may be centrally collected and subjected to quality checks and review by a central imaging vendor at the discretion of Salarius.

Trial Locations

Locations (15)

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Sarcoma Oncology Research Center; 🇺🇸 Santa Monica, California, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

The Research Institute at Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

H. Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

Johns Hopkins All Children's Hospital; 🇺🇸 Saint Petersburg, Florida, United States

Cleveland Clinic Taussig Cancer Institute; 🇺🇸 Cleveland, Ohio, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Oregon Health Sciences University; 🇺🇸 Portland, Oregon, United States