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

Sarcoma Clinical Trial

— HopES  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03778996
• Other study ID #: SM-88-JAF-16
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 3, 2020
• Est. completion date: March 31, 2025

Study information

• Verified date: April 2024
• Source: Sarcoma Oncology Research Center, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 31
• Est. completion date: March 31, 2025
• Est. primary completion date: December 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neuroectodermal Tumors, Primitive, Peripheral
• Sarcoma
• Sarcoma, Ewing

Intervention

Drug:
• Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)
Daily oral combination therapy for cancer

Locations

Country	Name	City	State
United States	Sarcoma Oncology Research Center	Santa Monica	California

Sponsors (2)

Lead Sponsor	Collaborator
Sarcoma Oncology Research Center, LLC	Tyme, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1	Every 3 months for up to 2 years
Primary	Stable Disease for at Least 3 Months	Stable disease (SD) as evaluated using RECIST 1.1	Every 3 months for up to 2 years
Primary	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	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
Secondary	Overall Survival	From date enrollment until the date of death	Every 3 months for up to 2 years
Secondary	Clinical Benefit Rate	CR+PR+SD as evaluated using RECIST 1.1	Every 3 months for up to 2 years
Secondary	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

External Links

•   Sarcoma Oncology Research Center