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

NCT03778996 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: SM-88-JAF-16
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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 (up to 12 per cohort) will be enrolled. Study patients will receive oral SM-88, with scheduled safety and efficacy evaluations.

Conditions

Sarcoma, Ewing; Sarcoma

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate

  Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1

  Every 3 months for up to 2 years

• Stable Disease for at Least 3 Months

  Stable disease (SD) as evaluated using RECIST 1.1

  Every 3 months for up to 2 years

• Progression Free Survival on Study of at Least 1.5 Times the Duration of PFS for the Last Prior Treatment

  From date of enrollment until the date of first documented progression, as evaluated using RECIST 1.1, or date of death, whichever occurs first

  Every 3 months for up to 2 years

Secondary Outcomes (4)

• Duration of Response

  Every 3 months for up to 2 years

• Overall Survival

  Every 3 months for up to 2 years

• Clinical Benefit Rate

  Every 3 months for up to 2 years

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5

  From date of enrollment until 28 days after last treatment with SM-88

Study Arms (2)

Maintenance Treatment: Ewing's Sarcoma

EXPERIMENTAL

Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus

Drug: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)

Salvage Treatment: Sarcoma

EXPERIMENTAL

Combination metyrosine-derivative, low-dose methoxasalen, phenytoin and sirolimus

Drug: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)

Interventions

Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS) DRUG

Daily oral combination therapy for cancer

Also known as: SM-88

Maintenance Treatment: Ewing's Sarcoma; Salvage Treatment: Sarcoma

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to provide written informed consent to participate in this study
• ≥12 years of age
• Diagnosis:
• Maintenance treatment cohort: Histologic or cytologic diagnosis of Ewing's sarcoma, including non-resected, locally advanced or metastatic disease
• 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
• Radiographic disease assessment within 35 days prior to enrollment and planned treatment start with study drug
• Prior treatment:
• Maintenance treatment cohort : 1-3 prior lines of systemic treatment (including current treatment)
• Salvage cohort: Any number of prior treatments
• Maintenance treatment cohort only: Patient completed current line of treatment (systemic, surgery, radiation) prior to enrollment, without disease progression as compared to baseline AND has achieved at least one of the following
• CR in response to current second or third line treatment
• PR in response to current line of treatment (after at least 4 cycles, if treatment included systemic therapy)
• SD in response to current line of treatment (after at least 4 cycles, if treatment included systemic therapy)
• Measurable disease, except for patients in Cohort A who have achieved CR at the conclusion of current 2nd or 3rd line of treatment
• ECOG performance status 0-2

You may not qualify if:

• Systemic anticancer agents within 14 days prior to treatment on study
• Major surgery within 30 days
• Prior treatment with SM-88
• 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
• History of any drug allergies or significant adverse reactions to any of the components of SM-88
• History of light sensitive diseases for which methoxsalen would be contraindicated
• Current or anticipated treatment with a contraindicated medication
• Evidence of viral infections including human immunodeficiency virus (HIV), hepatitis B, and hepatitis C

Sponsors & Collaborators

• Sarcoma Oncology Research Center, LLC: lead
• Tyme, Inc: collaborator

Study Sites (1)

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Related Links

• Sarcoma Oncology Research Center

MeSH Terms

Conditions

Sarcoma, Ewing; Sarcoma

Interventions

Methoxsalen; Phenytoin; Sirolimus; racemetyrosine

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Furocoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Hydantoins; Imidazolidines; Imidazoles; Azoles; Macrolides; Lactones; Organic Chemicals

Study Officials

• Sant P Chawla, MD

  Sarcoma Oncology Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: December 19, 2018
• Study Start: January 3, 2020
• Primary Completion (Estimated): December 19, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)