Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing Sarcoma
- Patients must have a histologic confirmed diagnosis of Ewing sarcoma that is refractory or recurrent 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.
- Expansion Phase Only: 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. Note: Patients do not need to have measurable disease in either the accelerated or 3+3 cohorts.
- Patients must have had prior camptothecin-based regimen, have a contraindication to camptothecin-based regimen, or declined treatment with a camptothecin-based regimen.
- 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.
- Patients must have normal organ and marrow function
- Archival tumor tissue available for translocation analysis or willingness to provide tumor biopsy during screening.
- Willingness to provide tumor biopsies during screening and while on treatment (Dose expansion cohort only). Optional for patients < 18 years of age.
- Ability to understand and the willingness to sign a written informed consent document.
- Patients who have not recovered to grade 1 or baseline from adverse events related to prior therapy excluding lymphopenia, alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3.
- Patients who are receiving any other investigational agents.
- Prior therapy with LSD1 targeted agents including monoamine oxidases for cancer therapy.
- Prior systemic anti-cancer treatment (chemotherapy, biologic therapy [ie. small molecular inhibitors, monoclonal antibodies]) within 21 days prior to Cycle 1 Day 1.
- Prior therapy with immunotherapy such as a checkpoint inhibitor, cellular therapy or vaccine therapy within 28 days prior to Cycle 1 Day 1.
- 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 Day1).
- Prior therapy with long acting myeloid growth factor within 14 days or 7 days from a short acting myeloid growth factor.
- Evidence of graft versus host disease or prior allo- or auto-bone marrow transplant (BMT) or stem cell infusion within 84 days from Cycle 1 Day 1 or receiving immunosuppression 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.
- Patients with 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.
- Patients 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: ongoing or active infection; transfusion dependent thrombocytopenia or anemia; psychiatric illness/social situations that would limit compliance with study requirements
- Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following: symptomatic congestive heart failure; Left Ventricular Ejection Fraction (LVEF) ≤ 50%; unstable angina pectoris or cardiac arrhythmia; baseline QTc ≥ 450 milliseconds; Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome
- Any major surgery within 21 days prior to Cycle 1 Day 1.
- Pregnant and breastfeeding women
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SP-2577. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
This phase 1 study is an open-label, non-randomized dose escalation study of SP-2577 administered orally in patients with refractory or recurrent Ewing sarcoma. The study design is based on a Simon's 4B design.
Trial Phase Phase I
Trial Type Treatment
Salarius Pharmaceuticals, LLC
- Primary ID SALA-002-EW16
- Secondary IDs NCI-2018-01744
- Clinicaltrials.gov ID NCT03600649