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

Status: Active

Description

Phase 1, open-label, non-randomized dose finding study of SP-2577 in patients with refractory or recurrent Ewing sarcoma.

Eligibility Criteria

Inclusion Criteria

  • 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.
  • Patients 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, see Appendix A, 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 on and off treatment (Tier 2: Dose expansion cohort only). Optional for patients <18 years of age.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

  • 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. 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 study chair.
  • 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.
  • Patients 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
  • 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 are excluded from this study. The effects of SP-2577 on the developing human fetus have the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SP-2577.
  • 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. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of SP-2577 administration.
  • 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.

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Damon Russell Reed
Phone: 813-745-3242
Email: damon.reed@moffitt.org

Massachusetts

Boston
Boston Children's Hospital
Status: Active
Contact: Steven G. DuBois
Phone: 617-632-5460
Email: steven_dubois@dfci.harvard.edu
Brigham and Women's Hospital
Status: Active
Contact: Steven G. DuBois
Phone: 617-632-5460
Email: steven_dubois@dfci.harvard.edu
Dana-Farber Cancer Institute
Status: Active
Contact: Steven G. DuBois
Phone: 617-632-5460
Email: steven_dubois@dfci.harvard.edu
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Edwin Choy
Phone: 617-643-0230
Email: echoy@mgh.harvard.edu

Ohio

Columbus
Nationwide Children's Hospital
Status: In review
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

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 & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Salarius Pharmaceuticals, LLC

Trial IDs

Primary ID SALA-002-EW16
Secondary IDs NCI-2018-01744
Clinicaltrials.gov ID NCT03600649