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

• ClinicalTrials.gov Identifier: NCT03778996
• Recruitment Status: Active, not recruiting
• First Posted: December 19, 2018
• Last Update Posted: January 23, 2023
• Sponsor: Sarcoma Oncology Research Center, LLC
• Collaborator: Tyme, Inc
• Information provided by (Responsible Party): Sarcoma Oncology Research Center, LLC

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sarcoma, Ewing; Sarcoma	Drug: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 3, 2020
• Actual Primary Completion Date: January 19, 2023
• Estimated Study Completion Date: October 31, 2023

Arms and Interventions

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 Name: 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 Name: SM-88

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate [ Time Frame: Every 3 months for up to 2 years ]
   Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1
2. Stable Disease for at Least 3 Months [ Time Frame: Every 3 months for up to 2 years ]
   Stable disease (SD) as evaluated using RECIST 1.1
3. Progression Free Survival on Study of at Least 1.5 Times the Duration of PFS for the Last Prior Treatment [ Time Frame: Every 3 months for up to 2 years ]
   From date of enrollment until the date of first documented progression, as evaluated using RECIST 1.1, or date of death, whichever occurs first

Secondary Outcome Measures :

1. Duration of Response [ Time Frame: Every 3 months for up to 2 years ]
   From date of CR or PR until the date of first documented progression, as evaluated using RECIST 1.1
2. Overall Survival [ Time Frame: Every 3 months for up to 2 years ]
   From date enrollment until the date of death
3. Clinical Benefit Rate [ Time Frame: Every 3 months for up to 2 years ]
   CR+PR+SD as evaluated using RECIST 1.1
4. 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 ]
   Adverse events will be assessed at each visit and at unscheduled visits as clinically indicated

Eligibility Criteria

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

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 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

Contacts and Locations

Locations

United States, California

Sarcoma Oncology Research Center

Santa Monica, California, United States, 90403

Sponsors and Collaborators

Sarcoma Oncology Research Center, LLC

Tyme, Inc

Investigators

• Principal Investigator: Sant P Chawla, MD; Sarcoma Oncology Research Center

More Information

Additional Information:

Sarcoma Oncology Research Center 

• Responsible Party: Sarcoma Oncology Research Center, LLC
• ClinicalTrials.gov Identifier: NCT03778996
• Other Study ID Numbers: SM-88-JAF-16
• First Posted: December 19, 2018
• Last Update Posted: January 23, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sarcoma Oncology Research Center, LLC:

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

Additional relevant MeSH terms:

Sarcoma; Sarcoma, Ewing; Neuroectodermal Tumors, Primitive, Peripheral; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Sirolimus; Phenytoin; Methoxsalen; alpha-Methyltyrosine; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Antifungal Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers