Phase 1 Trial of the LSD1 Inhibitor Seclidemstat (SP 2577) with and without Topotecan and Cyclophosphamide in Patients with Relapsed or Refractory Ewing Sarcoma and Select Sarcomas
The purpose of this study is to evaluate the safety and tolerability of SP-2577 in patients with relapsed or refractory Ewing sarcoma.
Primary Objective: To evaluate the safety and tolerability of SP-2577 in patients with relapsed or refractory Ewing sarcoma.
Secondary Objectives: To determine the MTD of SP-2577 in patients with refractory or recurrent Ewing sarcoma. To characterize pharmacokinetics of SP-2577. To evaluate the anti-tumor activity of SP-2577 in patients with refractory or recurrent Ewing sarcoma.
Exploratory Objective: Explore the use of circulating tumor cells (CTC), cell-free DNA (cfDNA) and Hemoglobin F as pharmacodynamic markers of disease burden, drug effect, and tumor response.
Participants 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.
Must have radiographic evidence of disease. Patients must have disease evaluable by Response Evaluation Criteria in Solid Tumors (RECIST)1.1. Bone only disease that has been biopsy-proven is acceptable during dose escalation but not expansion phase.
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.
Normal organ and marrow function
Archival tumor tissue available for translocation analysis or willingness to provide tumor biopsy during
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
Ability to understand and the willingness to sign a written informed consent document.
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 Lysine Specific Demethlase 1 (LSD1) targeted agents including monoamine oxidases for cancer therapy.
Prior systemic anti-cancer treatment (chemotherapy, biologic therapy [i.e., small molecular inhibitors, 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.
Prior therapy with immunotherapy such as a checkpoint inhibitor, cellular therapy or vaccine within 42 days prior to Cycle 1 Day 1.
Prior small port palliative radiotherapy within 14 days or 42 days from definitive local control radiation (any dose greater than 50Gy).
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.
Currently receiving any of the following substances and cannot be discontinued 14 days 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
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