Description:
Phase 1, open-label, non-randomized dose finding study of SP-2577 in patients with refractory
or recurrent Ewing sarcoma.
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
Interventions
Drug | Synonyms | Arms |
---|
SP-2577 | LSD1 Inhibitor | SP-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
Name | Type | Description | Interventions |
---|
SP-2577 | Experimental | Twice-daily administration of oral 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 19, 2020