MPS Therapy for Sarcoma

(HopES Trial)

Overseen By Sant P Chawla, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Sarcoma Oncology Research Center, LLC

Must not be taking: Systemic anticancer agents

Disqualifiers: Major surgery, Viral infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 29

Duration: Up to 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of SM-88, a new oral cancer treatment, in individuals with advanced sarcomas, including Ewing's Sarcoma. Researchers are studying two groups: those without disease progression after previous treatments and those needing new options after other treatments failed. SM-88 combines several drugs to target cancer cells in different ways. Individuals with advanced sarcoma that hasn’t improved with standard treatments and who can swallow pills might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering access to promising new therapies.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any systemic anticancer agents at least 14 days before starting the study treatment. If you are on other medications, the protocol does not specify, but you should discuss this with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SM-88, a combination of several drugs, has undergone previous testing. In one study, about 24% of patients experienced stable disease, meaning their condition did not worsen. This suggests the treatment was effective for many patients. Importantly, the study found that patients maintained their quality of life while on this treatment, indicating a positive safety profile.

As a phase 2 trial, the treatment has already been tested in people to some extent. This phase focuses on assessing efficacy and safety. While specific details on side effects aren't provided, the maintenance of quality of life suggests that serious side effects might not be common. However, staying updated on any new findings as the trial progresses is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for sarcoma?

Researchers are excited about SM-88 for sarcoma because it uses a unique combination of compounds that work together in a novel way. Unlike standard treatments like chemotherapy and radiation, SM-88 combines a metyrosine-derivative with low-dose methoxsalen, phenytoin, and sirolimus to target cancer cells. This combination is designed to disrupt cancer cell metabolism and enhance the immune response, potentially leading to improved effectiveness and fewer side effects. By focusing on these mechanisms, SM-88 offers a fresh approach to tackling sarcoma, which could provide new hope for patients.

What evidence suggests that this trial's treatments could be effective for sarcoma?

Research has shown that SM-88, a treatment composed of four different drugs, offers potential benefits for treating advanced Ewing's Sarcoma and other sarcomas. In an earlier study, about 24% of patients experienced stable disease, meaning their cancer did not worsen. Although no patients experienced a complete or partial reduction in their cancer, the treatment helped maintain their quality of life. In this trial, participants will receive a combination of metyrosine-derivative, low-dose methoxsalen, phenytoin, and sirolimus, which together form SM-88. SM-88 works by interfering with the way cancer cells use energy, which is crucial for their growth. While it's still early, these findings suggest that SM-88 might help manage advanced sarcoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Sant P Chawla, MD

Principal Investigator

Sarcoma Oncology Research Center

Are You a Good Fit for This Trial?

This trial is for people aged ≥12 with advanced Ewing's Sarcoma or other sarcomas, who've had up to three prior treatments. They must have stable disease after their latest treatment or a partial/full response without progression. Participants need good organ function and an ECOG performance status of 0-2, meaning they can care for themselves and are up and about more than half the day.

Inclusion Criteria

Radiographic disease assessment within 35 days prior to enrollment and planned treatment start with study drug

Adequate organ function defined as all laboratory parameters ≤ Grade 2 NCI CTCAE criteria

1-3 prior lines of systemic treatment (including current treatment) for maintenance treatment cohort

Exclusion Criteria

Evidence of viral infections including human immunodeficiency virus (HIV), hepatitis B, and hepatitis C

Major surgery within 30 days

Current or anticipated treatment with a contraindicated medication

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral treatment with SM-88 in continuous 28-day cycles

Up to 48 weeks

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term Follow-up

Participants are monitored for overall survival and clinical benefit rate

Every 3 months for up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• SM-88

Trial Overview The trial tests SM-88 (a mix of metyrosine-derivative, methoxsalen, phenytoin, sirolimus) in patients with advanced Ewing's Sarcoma post-treatment without disease progression and those needing salvage therapy for any sarcoma. Up to 24 patients will take oral SM-88 with regular safety checks and assessments of its effectiveness.

How Is the Trial Designed?

Group I: Salvage Treatment: Sarcoma Experimental Treatment 1 Intervention

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

Group II: Maintenance Treatment: Ewing's Sarcoma Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Sarcoma Oncology Research Center, LLC

Lead Sponsor

Trials

9

Recruited

910+

Joseph Ahmed Foundation

Collaborator

Trials

1

Recruited

30+

Tyme, Inc

Industry Sponsor

Trials

5

Recruited

200+

Published Research Related to This Trial

MK1775, a Wee1 inhibitor, shows promising therapeutic efficacy in treating sarcomas by inducing apoptotic cell death and enhancing the effects of gemcitabine, a commonly used chemotherapy drug, in various sarcoma cell lines and patient-derived samples.

The study demonstrated that MK1775 has a high safety profile and effectively induces significant cell death in a mouse model of osteosarcoma, suggesting its potential as a new treatment option for both adult and pediatric sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wee1 inhibition by MK-1775 leads to tumor inhibition and enhances efficacy of gemcitabine in human sarcomas. Kreahling, JM., Foroutan, P., Reed, D., et al.[2022]

A new combination treatment strategy using the CDK4/6 inhibitor palbociclib shows promise for treating Rb-positive soft tissue sarcomas by inducing cell cycle arrest, making the cancer cells more sensitive to other treatments like doxorubicin.

This synergistic effect was confirmed in both laboratory tests and in vivo studies using patient-derived xenografts, providing strong preclinical support for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest. Francis, AM., Alexander, A., Liu, Y., et al.[2022]

Ecteinascidin-743 (ET-743) demonstrated antitumoral activity in advanced soft tissue sarcoma patients, with a 4% overall response rate and a 24% disease progression control rate at 6 months, indicating some effectiveness in a challenging patient population.

The treatment had a manageable safety profile, although 50% of patients experienced significant liver enzyme elevations and 61% had severe neutropenia, with two treatment-related deaths occurring due to complications likely linked to protocol violations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. Yovine, A., Riofrio, M., Blay, JY., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03778996

SM-88 Maintenance Therapy for Advanced Ewing's ... The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer treatment, measured as positive efficacy events, including overall ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9678093/

A randomized phase II study of SM‐88 plus methoxsalen ... Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality‐of‐life (QOL) was maintained and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468124523000086

Ewing sarcoma genomics and recent therapeutic ... Patients with localized disease currently have a 5-year survival rate of approximately 70% when receiving VACD-IE chemotherapy regimens (vancristine, ...

4. withpower.com withpower.com/trial/mps-therapy-for-sarcoma-96306

MPS Therapy for Sarcoma · Info for Participants Trial Overview The trial tests SM-88 (a mix of metyrosine-derivative, methoxsalen, phenytoin, sirolimus) in patients with advanced Ewing's Sarcoma post- ...

5. smartpatients.com smartpatients.com/trials/NCT03778996

SM-88 Maintenance Therapy for Advanced Ewing's ... The primary objective is to evaluate the efficacy of SM-88, a combination metabolic cancer treatment, in two study cohorts: - Clinically advanced Ewing's ...

6. barchart.com barchart.com/story/news/33694066/ewing-sarcoma-pipeline-outlook-report-2025-key-25-companies-and-breakthrough-therapies-shaping-the-future-landscape

Ewing Sarcoma Pipeline Outlook Report 2025: Key 25 ... DelveInsight's, “Ewing Sarcoma Pipeline Insights” report provides comprehensive insights about 25+ Ewing Sarcoma companies and 25+ pipeline ...