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

NCT03600649 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: SALA-002-EW16
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 16

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

Conditions

Ewing Sarcoma; Myxoid Liposarcoma; Sarcoma,Soft Tissue; Desmoplastic Small Round Cell Tumor; Extraskeletal Myxoid Chondrosarcoma; Angiomatoid Fibrous Histiocytoma; Clear Cell Sarcoma; Primary Pulmonary Myxoid Sarcoma; Myoepithelial Tumor; Sclerosing Epithelioid Fibrosarcoma; Fibromyxoid Tumor

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  From screening through at least 30 days after end of treatment, up to approximately 24 months

Secondary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

Myxoid Liposarcoma

EXPERIMENTAL

Twice-daily administration of oral seclidemstat

Drug: Seclidemstat

Sarcomas with FET-family translocations, including demoplastic small round cell tumors

EXPERIMENTAL

Twice-daily administration of oral seclidemstat

Drug: Seclidemstat

Ewing sarcoma, combination therapy

EXPERIMENTAL

Twice daily administration of seclidemstat in combination with cyclophosphamide and topotecan

Drug: Seclidemstat; Drug: Cyclophosphamide; Drug: Topotecan

Interventions

Seclidemstat DRUG

Twice daily administration of seclidemstat

Also known as: LSD1 Inhibitor, SP-2577

Ewing sarcoma, combination therapy; Myxoid Liposarcoma; Sarcomas with FET-family translocations, including demoplastic small round cell tumors

Cyclophosphamide DRUG

250 mg/m2/day on Days 1 thru 5 of a 21-day cycle

Ewing sarcoma, combination therapy

Topotecan DRUG

0.75 mg/m2/day on Days 1 thru 5 of a 21-day cycle

Ewing sarcoma, combination therapy

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 12 years and weight ≥ 40 kg.
• Karnofsky ≥ 70% for over ≥ 16 years old and Lansky ≥ 70% for under 16 years old, equivalent to Eastern Cooperative Oncology Group (ECOG) performance status Grade 0 or 1.
• Life expectancy of greater than 4 months in investigator's opinion.
• Willingness to provide tumor biopsies during screening and while on treatment. Optional for patients \< 18 years of age and patients enrolled in the Ewing sarcoma combination treatment arm. Biopsies can be exempt if deemed by the investigator that the biopsy is not medically feasible for the patient or the patient is unfit for the procedure.
• Normal organ and marrow function as defined below:
• absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• platelets ≥ 100 x 109/L; no transfusion 7 days prior to labs
• total bilirubin ≤ 1.5 x upper limit of normal (ULN) or, in patients with Gilbert syndrome, total bilirubin \> 1.5 x ULN as long as direct bilirubin is normal
• AST and ALT ≤ 3 x ULN
• creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above normal
• Ability to understand and the willingness to sign a written informed consent document.
• Patients must have a histologic confirmed diagnosis of Ewing sarcoma with a known EWSR1 translocation through local assessment that is relapsed or refractory and must have received at least one prior course of therapy for Ewing sarcoma. For the purposes of this study, refractory disease is defined as metastatic or unresectable disease that has either progressed or is stable at completion of planned therapy.
• Patients must have had no more than 2 lines/courses of systemic treatment for Ewing sarcoma
• No prior therapy with the combination regimen of topotecan and cyclophosphamide. Prior cyclophosphamide is allowed if not combined with topotecan.
• Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

You may not qualify if:

• Patients receiving therapy with other anti-neoplastic or experimental agents.
• Prior therapy with LSD1 targeted agents including monoamine oxidases for cancer therapy.
• Prior oral tyrosine kinase inhibitors (i.e. sorafenib, pazopanib, regorafenib, cabozantanib) within 14 days of Cycle 1 Day 1.
• Other, prior systemic anti-cancer treatment (chemotherapy or biologic therapy \[i.e. monoclonal antibodies\]) within 21 days prior to Cycle 1 Day 1. For agents that have known adverse events occurring beyond 21 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Medical Monitor.
• Prior therapy with immunotherapy such as a checkpoint inhibitor, cellular therapy or vaccine therapy within 28 days prior to Cycle 1 Day 1. Patients must have recovered from any immune-related adverse events to Grade 1 or baseline and require ≤ 10 mg of prednisone equivalent daily. Patients with immune-related hypothyroidism and/or hypoadrenalism may enroll while on thyroid or hydrocortisone replacement therapy, respectively.
• Prior small port palliative radiotherapy within 14 days of Cycle 1 Day 1 or within 42 days of Cycle 1 Day 1 from definitive local control radiation (any dose greater than 50 Gy, within 42 days of Cycle 1 Day 1).
• Prior therapy with long acting myeloid growth factor within 14 days of Cycle 1 Day 1 or within 7 days of Cycle 1 Day 1 from a short acting myeloid growth factor.
• Evidence of graft versus host disease or prior allo- or auto-bone marrow transplant or stem cell infusion within 84 days from Cycle 1 Day 1 or receiving immunosuppressants following a stem cell procedure.
• Participation in a prior investigational study within 30 days prior to Cycle 1 Day 1 or within 5 half-lives of the investigational product, whichever is longer.
• Progressive or symptomatic brain metastases; patients with brain metastases may be included in this trial as long as the brain metastases have received definitive treatment and are stable (i.e., no evidence of progression). The brain metastases must be stable for a minimum of 6 weeks prior to Cycle 1 Day 1.
• Currently receiving any of the following substances and cannot be discontinued 14 days or 5 half-lives for CYP inhibitors (whichever is shorter) prior to Cycle 1 Day 1:
• moderate or strong inhibitors or inducers of major CYP isoenzymes, including grapefruit, grapefruit hybrids, pomelos, star fruit, and Seville oranges
• moderate or strong inhibitors or inducers of major drug transporters
• substrates of CYP3A4/5 with a narrow therapeutic index
• Uncontrolled concurrent illness including, but not limited to:

Sponsors & Collaborators

• Salarius Pharmaceuticals, LLC: lead
• National Pediatric Cancer Foundation: collaborator

Study Sites (16)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

The Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 77030, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Sarcoma, Ewing; Liposarcoma, Myxoid; Sarcoma; Desmoplastic Small Round Cell Tumor; Chondrosarcoma, Extraskeletal Myxoid; Histiocytoma, Angiomatoid Fibrous; Sarcoma, Clear Cell; Myoepithelioma; Fibroma

Interventions

seclidemstat; Cyclophosphamide; Topotecan

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Complex and Mixed; Neoplasms, Fibrous Tissue

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two cohorts with single-agent seclidemstat in patients with myxoid liposarcoma and in patients with other sarcomas with similar chromosomal translocations to Ewing sarcoma (FET-family translocations), and one cohort of Ewing sarcoma patients treated with seclidemstat in combination with topotecan and cyclophosphamide

Study Record Dates

• First Submitted: June 4, 2018
• First Posted: July 26, 2018
• Study Start: June 4, 2018
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 21, 2023

Record last verified: 2023-11

Locations

US (16)