Clinical Trials /

Phase 1 Trial of the LSD1 Inhibitor SP-2577 (Seclidemstat) in Patients With Advanced Solid Tumors

NCT03895684

Description:

Phase 1, open-label, non-randomized dose finding study of SP-2577 in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Trial of the LSD1 Inhibitor SP-2577 (Seclidemstat) in Patients With Advanced Solid Tumors
  • Official Title: Phase 1 Trial of the LSD1 Inhibitor SP-2577 (Seclidemstat) in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: SALA-003-AC19
  • NCT ID: NCT03895684

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
SP-2577 SeclidemstatLSD1 InhibitorSp-2577

Purpose

Phase 1, open-label, non-randomized dose finding study of SP-2577 in patients with advanced solid tumors.

Detailed Description

      Phase 1, open-label, non-randomized dose finding study of SP-2577 given as oral tablets in
      patients with advanced solid tumors in 28-day cycles. The study design is based on a Simon's
      4B design without intrapatient dose escalation.
    

Trial Arms

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

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 12 years and weight ≥ 40 kg.

          -  Diagnosis of advanced or recurrent, histologically or cytologically confirmed, solid
             malignancy that is either metastatic or unresectable. At time of enrollment, subjects
             must have progressed on, be intolerant of, refuse, or ineligible for, all available
             standard of care therapies.

          -  Subjects must demonstrate measurable disease per Response Evaluation Criteria in Solid
             Tumors (RECIST) v1.1, with the exception of castration-resistant prostate cancer
             (CRPC) who should have progression based on the PCWG 3.0 criteria

          -  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

          -  Willingness to provide tumor biopsies of assessible lesions on and off treatment (Dose
             expansion cohort only). Optional for patients <18 years of age.

          -  Able to swallow and retain orally administered medication.

          -  Patients must have normal organ and marrow function

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Subjects with Ewing Sarcoma. See NCT03600649, Protocol Number: SALA-002-EW16.

          -  Subjects with primary central nervous system tumors

          -  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 (Version 5.0).

          -  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. Patients must have recovered
             from any immune-related adverse events to grade 1 or baseline and require ≤ 10 mg of
             prednisone equivalents daily. Patients with immune-related hypothyroidism and/or
             hypoadrenalism may enroll while on thyroid or hydrocortisone replacement therapy,
             respectively.

          -  Prior small port palliative radiotherapy within 14 days or 42 days from definitive
             local control radiation (any dose greater than 50Gy).

          -  Anti-androgen therapies for prostate cancer, such as bicalutamide, within 4 weeks
             prior to enrollment. Second-line hormone therapies such as enzalutamide, abiraterone,
             or orteronel within 2 weeks prior to enrolment. Subjects with prostate cancer should
             remain on luteinizing hormone releasing hormone (LHRH) agonists or antagonists.
             Subjects with prostate cancer may also remain on low-dose prednisone or prednisolone
             up to 10 mg/day

          -  Prior therapy with long acting myeloid growth factor within 14 days or 7 days from a
             short acting myeloid growth factor.

          -  Participation in a prior investigational study within 30 days prior to Cycle 1 Day 1.

          -  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 must have discontinued anti-seizure medications and steroids, except for
             physiologic steroid dosing (≤10 mg/day of prednisone equivalents).

          -  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 QTcF (Fridericia) ≥ 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
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 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 conditions
Measure:Characterization of 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 conditions
Measure:Characterization of 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 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 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 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
Measure: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
Safety Issue:
Description:Determine changes serum hemoglobin F concentrations correlated with SP-2577 treatment and clinical and radiographic markers of disease burden (either response or resistance/progression).
Measure: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
Safety Issue:
Description: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.

Details

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

Last Updated

October 31, 2019