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

Primary Purpose

Sarcoma, Ewing, Sarcoma

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Sarcoma, Ewing focused on measuring Ewing's Sarcoma, Locally advanced sarcoma, Metastatic sarcoma, SM-88, D.L-alpha-metyrosine

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Ability to understand and willingness to provide written informed consent to participate in this study
≥12 years of age
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
Radiographic disease assessment within 35 days prior to enrollment and planned treatment start with study drug
Prior treatment:
1. Maintenance treatment cohort : 1-3 prior lines of systemic treatment (including current treatment)
2. Salvage cohort: Any number of prior treatments
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)
Measurable disease, except for patients in Cohort A who have achieved CR at the conclusion of current 2nd or 3rd line of treatment
ECOG performance status 0-2
Adequate organ function defined as all laboratory parameters ≤ Grade 2 NCI CTCAE criteria
Patients must be able to swallow and retain whole capsules

Key Exclusion Criteria:

Systemic anticancer agents within 14 days prior to treatment on study
Major surgery within 30 days
Prior treatment with SM-88
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
History of any drug allergies or significant adverse reactions to any of the components of SM-88
History of light sensitive diseases for which methoxsalen would be contraindicated
Current or anticipated treatment with a contraindicated medication
Evidence of viral infections including human immunodeficiency virus (HIV), hepatitis B, and hepatitis C

Sites / Locations

Sarcoma Oncology Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Maintenance Treatment: Ewing's Sarcoma

Salvage Treatment: Sarcoma

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall Response Rate

Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1

Stable Disease for at Least 3 Months

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

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

Duration of Response

From date of CR or PR until the date of first documented progression, as evaluated using RECIST 1.1

Overall Survival

From date enrollment until the date of death

Clinical Benefit Rate

CR+PR+SD as evaluated using RECIST 1.1

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

Full Information

NCT ID

NCT03778996

First Posted

December 6, 2018

Last Updated

January 19, 2023

Sponsor

Sarcoma Oncology Research Center, LLC

Collaborators

Tyme, Inc

1. Study Identification

Unique Protocol Identification Number

NCT03778996

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

January 3, 2020 (Actual)

Primary Completion Date

January 19, 2023 (Actual)

Study Completion Date

October 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sarcoma Oncology Research Center, LLC

Collaborators

Tyme, Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sarcoma, Ewing, Sarcoma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

31 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Maintenance Treatment: Ewing's Sarcoma

Arm Type

Experimental

Arm Description

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

Arm Title

Salvage Treatment: Sarcoma

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

SM-88

Intervention Description

Daily oral combination therapy for cancer

Primary Outcome Measure Information:

Title

Overall Response Rate

Description

Complete response (CR) + partial response (PR) as evaluated using RECIST 1.1

Time Frame

Every 3 months for up to 2 years

Title

Stable Disease for at Least 3 Months

Description

Stable disease (SD) as evaluated using RECIST 1.1

Time Frame

Every 3 months for up to 2 years

Title

Progression Free Survival on Study of at Least 1.5 Times the Duration of PFS for the Last Prior Treatment

Description

From date of enrollment until the date of first documented progression, as evaluated using RECIST 1.1, or date of death, whichever occurs first

Time Frame

Every 3 months for up to 2 years

Secondary Outcome Measure Information:

Title

Duration of Response

Description

From date of CR or PR until the date of first documented progression, as evaluated using RECIST 1.1

Time Frame

Every 3 months for up to 2 years

Title

Overall Survival

Description

From date enrollment until the date of death

Time Frame

Every 3 months for up to 2 years

Title

Clinical Benefit Rate

Description

CR+PR+SD as evaluated using RECIST 1.1

Time Frame

Every 3 months for up to 2 years

Title

Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5

Description

Adverse events will be assessed at each visit and at unscheduled visits as clinically indicated

Time Frame

From date of enrollment until 28 days after last treatment with SM-88

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Ability to understand and willingness to provide written informed consent to participate in this study ≥12 years of age Diagnosis: Maintenance treatment cohort: Histologic or cytologic diagnosis of Ewing's sarcoma, including non-resected, locally advanced or metastatic disease 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 Radiographic disease assessment within 35 days prior to enrollment and planned treatment start with study drug Prior treatment: Maintenance treatment cohort : 1-3 prior lines of systemic treatment (including current treatment) Salvage cohort: Any number of prior treatments 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 CR in response to current second or third line treatment PR in response to current line of treatment (after at least 4 cycles, if treatment included systemic therapy) SD in response to current line of treatment (after at least 4 cycles, if treatment included systemic therapy) Measurable disease, except for patients in Cohort A who have achieved CR at the conclusion of current 2nd or 3rd line of treatment ECOG performance status 0-2 Adequate organ function defined as all laboratory parameters ≤ Grade 2 NCI CTCAE criteria Patients must be able to swallow and retain whole capsules Key Exclusion Criteria: Systemic anticancer agents within 14 days prior to treatment on study Major surgery within 30 days Prior treatment with SM-88 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 History of any drug allergies or significant adverse reactions to any of the components of SM-88 History of light sensitive diseases for which methoxsalen would be contraindicated Current or anticipated treatment with a contraindicated medication Evidence of viral infections including human immunodeficiency virus (HIV), hepatitis B, and hepatitis C

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sant P Chawla, MD

Organizational Affiliation

Sarcoma Oncology Research Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sarcoma Oncology Research Center

City

Santa Monica

State/Province

California

ZIP/Postal Code

90403

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://sarcomaoncology.com/

Description

Sarcoma Oncology Research Center

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

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