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

Phase 2 Clinical Trial to Evaluate Efficacy and Safety of SM-88 Used With Methoxsalen, Phenytoin, and Sirolimus (MPS) as Maintenance Therapy Following Standard Treatments for Ewing's Sarcoma or as Salvage Therapy for Advanced Sarcomas

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sarcoma; Sarcoma, Ewing
• Intervention / Treatment: Drug: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)

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

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 35 days prior to enrollment and planned treatment start with study drug

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) 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maintenance Treatment: Ewing's Sarcoma; Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus	Drug: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS); Daily oral combination therapy for cancer; Other Names: SM-88
Experimental: Salvage Treatment: Sarcoma; Combination metyrosine-derivative, low-dose methoxasalen, phenytoin and sirolimus	Drug: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS); Daily oral combination therapy for cancer; Other Names: SM-88

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sarcoma Oncology Research Center, LLC
• Collaborators: Tyme, Inc
• Investigators: Principal Investigator: Sant P Chawla, MD, Sarcoma Oncology Research Center

Publications and helpful links

Helpful Links

• Sarcoma Oncology Research Center

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2020
• Primary Completion (Estimated): December 19, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Ewing's Sarcoma; SM-88; Metastatic sarcoma; Locally advanced sarcoma; D.L-alpha-metyrosine
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive; Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive, Peripheral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Photosensitizing Agents; Dermatologic Agents; Anti-Bacterial Agents; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Antibiotics, Antineoplastic; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Sirolimus; Methoxsalen; Phenytoin; alpha-Methyltyrosine
• Other Study ID Numbers: SM-88-JAF-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No