Clinical Trials /

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

NCT03600649

Description:

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

Related Conditions:
  • Ewing Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing Sarcoma
  • Official Title: Phase 1 Trial of the LSD1 Inhibitor SP-2577 in Patients With Relapsed or Refractory Ewing Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: SALA-002-EW16
  • NCT ID: NCT03600649

Conditions

  • Ewing Sarcoma

Interventions

DrugSynonymsArms
SP-2577LSD1 InhibitorSP-2577

Purpose

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

Detailed Description

      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 Arms

NameTypeDescriptionInterventions
SP-2577ExperimentalTwice-daily administration of oral SP-2577
  • SP-2577

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.

          -  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.

        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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of SP-2577: Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0
Time Frame:From screening through at least 30 days after end of treatment, up to approximately 24 months
Safety Issue:
Description:Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0

Secondary Outcome Measures

Measure:Determine the maximum tolerated dose of SP-2577
Time Frame:DLTs within the first cycle of therapy (up to 28 days)
Safety Issue:
Description: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 (DLT).
Measure:Characterization of the pharmacokinetics of SP-2577
Time Frame:At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.
Safety Issue:
Description:area under the concentration time profile of SP-2577 under fasted and fed area under the concentration time profile of SP-2577 under fasted and fed conditions
Measure:Characterization of the pharmacokinetics of SP-2577
Time Frame:At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.
Safety Issue:
Description:time to maximum plasma concentration of SP-2577 under fasted and fed time to maximum plasma concentration of SP-2577 under fasted and fed conditions
Measure:Characterization of the pharmacokinetics of SP-2577
Time Frame:At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.
Safety Issue:
Description:maximum plasma concentration of SP-2577 under fasted and fed conditions
Measure:Characterization of the pharmacokinetics of SP-2577
Time Frame:At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.
Safety Issue:
Description:half-life of SP-2577 under fasted and fed conditions
Measure:Characterization of the pharmacokinetics of SP-2577
Time Frame:At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.
Safety Issue:
Description:clearance rate of SP-2577 under fasted and fed conditions
Measure:Characterization of the pharmacokinetics of SP-2577
Time Frame:At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.
Safety Issue:
Description:volume of distribution of SP-2577 under fasted and fed conditions
Measure:Efficacy parameter: overall response rate of SP-2577
Time Frame:From start of treatment through at least 30 days after end of treatment, up to approximately 24 months
Safety Issue:
Description:Assessed by radiographic imaging with response and progression evaluated by RECIST 1.1 guidelines
Measure:Efficacy parameter: duration of response of SP-2577
Time Frame:From start of treatment through at least 30 days after end of treatment, up to approximately 24 months
Safety Issue:
Description:Assessed by radiographic imaging with response and progression evaluated by RECIST 1.1 guidelines
Measure:Efficacy parameter: progression-free survival of SP-2577
Time Frame:From start of treatment through at least 30 days after end of treatment, up to approximately 24 months
Safety Issue:
Description:Assessed by radiographic imaging with response and progression evaluated by RECIST 1.1 guidelines and vital status information

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Salarius Pharmaceuticals, LLC

Last Updated

October 31, 2019