Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03600649
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : January 31, 2020
Sponsor:
Collaborator:
National Pediatric Cancer Foundation
Information provided by (Responsible Party):
Salarius Pharmaceuticals, LLC

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

Condition or disease Intervention/treatment Phase
Ewing Sarcoma Drug: SP-2577 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This single arm study will utilize an accelerated dose escalation, followed by a conventional 3+3 dose escalation phase to achieve maximum tolerated dose (MTD).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Trial of the LSD1 Inhibitor SP-2577 in Patients With Relapsed or Refractory Ewing Sarcoma
Actual Study Start Date : June 4, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: SP-2577
Twice-daily administration of oral SP-2577
Drug: SP-2577
Dose escalation and dose expansion of SP-2577
Other Name: LSD1 Inhibitor




Primary Outcome Measures :
  1. 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 ]
    Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0


Secondary Outcome Measures :
  1. Determine the maximum tolerated dose of SP-2577 [ Time Frame: DLTs within the first cycle of therapy (up to 28 days) ]
    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).

  2. 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. ]
    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

  3. 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. ]
    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

  4. 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. ]
    maximum plasma concentration of SP-2577 under fasted and fed conditions

  5. 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. ]
    half-life of SP-2577 under fasted and fed conditions

  6. 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. ]
    clearance rate of SP-2577 under fasted and fed conditions

  7. 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. ]
    volume of distribution of SP-2577 under fasted and fed conditions

  8. 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 ]
    Assessed by radiographic imaging with response and progression evaluated by RECIST 1.1 guidelines

  9. 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 ]
    Assessed by radiographic imaging with response and progression evaluated by RECIST 1.1 guidelines

  10. 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 ]
    Assessed by radiographic imaging with response and progression evaluated by RECIST 1.1 guidelines and vital status information


Other Outcome Measures:
  1. Changes in circulating tumor cells (CTCs) number [ Time Frame: At protocol defined time points from start of treatment through end of treatment, up to approximately 24 months ]
    Assessed by changes in CTC number correlated with SP-2577 treatment and clinical and radiographic markers of disease burden (either response or resistance/progression).

  2. Changes in circulating tumor cells (CTCs) RNA sequencing profiles [ Time Frame: At protocol defined time points from start of treatment through end of treatment, up to approximately 24 months ]
    Assessed by changes in the RNA sequencing profiles correlated with SP-2577 treatment and clinical and radiographic markers of disease burden (either response or resistance/progression).

  3. Changes in cell-free DNA (cfDNA) [ Time Frame: At protocol defined time points from start of treatment through end of treatment, up to approximately 24 months ]
    Determine changes in cfDNA levels correlated with SP-2577 treatment and clinical and radiographic markers of disease burden (either response or resistance/progression).

  4. Changes in serum hemoglobin F concentrations [ Time Frame: At protocol defined time points from start of treatment through end of treatment, up to approximately 24 months ]
    Determine changes serum hemoglobin F concentrations correlated with SP-2577 treatment and clinical and radiographic markers of disease burden (either response or resistance/progression).

  5. Changes in the molecular signatures of the tumor [ Time Frame: At protocol defined time points from start of treatment through end of treatment, up to approximately 24 months ]
    Assessed in dose expansion only by RNA-seq testing of tumor biopsy samples to determine changes in gene expression patterns by SP-2577 treatment to elucidate biological changes induced in the tumor by LSD1 inhibition.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03600649


Contacts
Layout table for location contacts
Contact: David S Wages, MD,PhD 508-740-7500 dwages@salariuspharma.com

Locations
Layout table for location information
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Magnolia Manzano         
Principal Investigator: Leo Mascarenhas, MD         
Sarcoma Oncology Research Center Recruiting
Santa Monica, California, United States, 90403
Contact: Victoria Chua-Alcala    310-552-9999    vchua@sarcomaoncology.com   
Principal Investigator: Sant P Chawla, MD         
United States, Florida
Johns Hopkins All Children's Hospital Recruiting
Saint Petersburg, Florida, United States, 33701
Contact: Jessica Crimella         
Principal Investigator: Jonathan Metts, MD         
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Principal Investigator: Damon Reed, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Morgan Krush         
Principal Investigator: Steven DuBois, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Principal Investigator: Paul Meyers, MD         
United States, Ohio
The Research Institute at Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Principal Investigator: Bhuvana Setty, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sherry Melton         
Principal Investigator: Douglas J Harrison, MD, MS         
Sponsors and Collaborators
Salarius Pharmaceuticals, LLC
National Pediatric Cancer Foundation
Investigators
Layout table for investigator information
Principal Investigator: Damon Reed, MD Moffitt Cancer Center

Layout table for additonal information
Responsible Party: Salarius Pharmaceuticals, LLC
ClinicalTrials.gov Identifier: NCT03600649    
Other Study ID Numbers: SALA-002-EW16
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: January 31, 2020
Last Verified: January 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue