Clinical Trials /

SM-88 as Maintenance Therapy for Advanced Ewing's Sarcoma Patients and as Salvage Therapy for Sarcoma Patients

NCT03778996

Description:

The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer treatment, in two study cohorts: - Clinically advanced Ewing's Sarcoma patients who have not progressed at the conclusion of systemic treatment - Clinically advanced sarcoma patients in the salvage treatment setting Up to 24 efficacy evaluable patients (12 per cohort) will be enrolled. Study patients will receive oral SM-88, with scheduled safety and efficacy evaluations.

Related Conditions:
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: SM-88 as Maintenance Therapy for Advanced Ewing's Sarcoma Patients and as Salvage Therapy for Sarcoma Patients
  • Official Title: A Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of SM-88 Used With Methoxsalen, Phenytoin, and Sirolimus (MPS) as Response Maintenance Therapy Following Standard Treatments for Patients With Ewing's Sarcoma or as Salvage Therapy for Patients With Clinically Advanced Sarcomas

Clinical Trial IDs

  • ORG STUDY ID: SM-88-JAF-16
  • NCT ID: NCT03778996

Conditions

  • Sarcoma, Ewing
  • Sarcoma

Interventions

DrugSynonymsArms
Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)SM-88Maintenance Treatment: Ewing's Sarcoma

Purpose

The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer treatment, in two study cohorts: - Clinically advanced Ewing's Sarcoma patients who have not progressed at the conclusion of systemic treatment - Clinically advanced sarcoma patients in the salvage treatment setting Up to 24 efficacy evaluable patients (12 per cohort) will be enrolled. Study patients will receive oral SM-88, with scheduled safety and efficacy evaluations.

Detailed Description

      This prospective, open-label, two stage, pilot phase 2 trial evaluates the efficacy and
      safety of SM-88 in two cohorts of patients: 1) as maintenance therapy following standard
      primary or palliative treatments for Ewing's sarcoma patients with high risk of relapse or
      disease progression; and 2) as salvage therapy for patients with clinically advanced
      sarcomas.

      The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer
      treatment, measured as positive efficacy events, including overall response, maintaining
      stable disease for ≥ 3 months, or progression free survival at least 1.5 times longer than
      the last prior line of treatment.

      Eligible patients will receive daily oral treatment with SM-88, which consists of
      D,L-alpha-metyrosine, used with methoxsalen, phenytoin, and sirolimus in continuous treatment
      cycles of 28 days. Treatment will continue until: 1) Symptomatic, clinical progression with
      radiographic progressive disease; 2) 48 weeks after documented complete response; or 3)
      evidence of unacceptable toxicity, or other decision to discontinue treatment
    

Trial Arms

NameTypeDescriptionInterventions
Maintenance Treatment: Ewing's SarcomaExperimentalCombination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus
  • Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)
Salvage Treatment: SarcomaExperimentalCombination metyrosine-derivative, low-dose methoxasalen, phenytoin and sirolimus
  • Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)

Eligibility Criteria

        Key Inclusion Criteria:

          1. Ability to understand and willingness to provide written informed consent to
             participate in this study

          2. ≥12 years of age

          3. Diagnosis:

               1. Maintenance treatment cohort: Histologic or cytologic diagnosis of Ewing's
                  sarcoma, including non-resected, locally advanced or metastatic disease

               2. Salvage treatment cohort: Non-resected, locally advanced or metastatic sarcoma
                  (including Ewing's sarcoma) for which there is no standard of care treatment and
                  no curative other option

          4. Radiographic disease assessment within 30 days prior to enrollment

          5. Prior treatment:

               1. Maintenance treatment cohort : 1-3 prior lines of systemic treatment (including
                  current treatment)

               2. Salvage cohort: Any number of prior treatments

          6. Maintenance treatment cohort only: Patient completed current line of treatment
             (systemic, surgery, radiation) within 30 days prior to enrollment, without disease
             progression as compared to baseline AND has achieved at least one of the following

               1. CR in response to current second or third line treatment

               2. PR in response to current line of treatment (after at least 4 cycles, if
                  treatment included systemic therapy)

               3. SD in response to current line of treatment (after at least 4 cycles, if
                  treatment included systemic therapy)

          7. Measurable disease, except for patients in Cohort A who have achieved CR at the
             conclusion of current 2nd or 3rd line of treatment

          8. ECOG performance status 0-2

          9. Adequate organ function defined as all laboratory parameters ≤ Grade 2 NCI CTCAE
             criteria

         10. Patients must be able to swallow and retain whole capsules

        Key Exclusion Criteria:

          1. Systemic anticancer agents within 14 days prior to treatment on study

          2. Major surgery within 30 days

          3. Prior treatment with SM-88

          4. Any screening laboratory, electrocardiogram (ECG), other clinical finding, comorbidity
             or clinical history that, in the opinion of the investigator, indicates an
             unacceptable risk for patient to participate in the study or would limit patient's
             ability to comply with study requirements

          5. History of any drug allergies or significant adverse reactions to any of the
             components of SM-88

          6. History of light sensitive diseases for which methoxsalen would be contraindicated

          7. Current or anticipated treatment with a contraindicated medication

          8. Evidence of viral infections including human immunodeficiency virus (HIV), hepatitis
             B, and hepatitis C
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:Every 3 months for up to 2 years
Safety Issue:
Description:Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1

Secondary Outcome Measures

Measure:Duration of Response
Time Frame:Every 3 months for up to 2 years
Safety Issue:
Description:From date of CR or PR until the date of first documented progression, as evaluated using RECIST 1.1
Measure:Overall Survival
Time Frame:Every 3 months for up to 2 years
Safety Issue:
Description:From date enrollment until the date of death
Measure:Clinical Benefit Rate
Time Frame:Every 3 months for up to 2 years
Safety Issue:
Description:CR+PR+SD as evaluated using RECIST 1.1
Measure:Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5
Time Frame:From date of enrollment until 28 days after last treatment with SM-88
Safety Issue:
Description:Adverse events will be assessed at each visit and at unscheduled visits as clinically indicated

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sarcoma Oncology Research Center, LLC

Trial Keywords

  • Ewing's Sarcoma
  • Locally advanced sarcoma
  • Metastatic sarcoma
  • SM-88
  • D.L-alpha-metyrosine

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