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

Tracking Information

• First Submitted Date: December 6, 2018
• First Posted Date: December 19, 2018
• Last Update Posted Date: January 23, 2023
• Actual Study Start Date: January 3, 2020
• Actual Primary Completion Date: January 19, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 17, 2018)

• 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
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 17, 2018)

• 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
• Overall Survival [ Time Frame: Every 3 months for up to 2 years ]
  From date enrollment until the date of death
• Clinical Benefit Rate [ Time Frame: Every 3 months for up to 2 years ]
  CR+PR+SD as evaluated using RECIST 1.1
• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SM-88 Maintenance Therapy for Advanced Ewing's Sarcoma and as Salvage Therapy for Sarcoma
• 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

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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Sarcoma, Ewing
• Sarcoma

Intervention

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

Daily oral combination therapy for cancer

Other Name: SM-88

Study Arms

• Experimental: Maintenance Treatment: Ewing's Sarcoma
  Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus
  Intervention: Drug: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)
• Experimental: Salvage Treatment: Sarcoma
  Combination metyrosine-derivative, low-dose methoxasalen, phenytoin and sirolimus
  Intervention: Drug: Combination metyrosine-derivative, low-dose methoxsalen, phenytoin and sirolimus (MPS)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 19, 2023): 31
• Original Estimated Enrollment (submitted: December 17, 2018): 24
• Estimated Study Completion Date: October 31, 2023
• Actual Primary Completion Date: January 19, 2023 (Final data collection date for primary outcome measure)

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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03778996
• Other Study ID Numbers: SM-88-JAF-16
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sarcoma Oncology Research Center, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Sarcoma Oncology Research Center, LLC
• Original Study Sponsor: Same as current
• Collaborators: Tyme, Inc

Investigators

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

• PRS Account: Sarcoma Oncology Research Center, LLC
• Verification Date: January 2023