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

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ClinicalTrials.gov Identifier: NCT03778996
Recruitment Status : Not yet recruiting
First Posted : December 18, 2018
Last Update Posted : April 11, 2019
Sponsor:
Collaborators:
Joseph Ahmed Foundation
Tyme, Inc
Information provided by (Responsible Party):
Sarcoma Oncology Research Center, LLC

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 (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 sirolimus, phenytoin and methoxsalen 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, phenytoin, methoxsalen, 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


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of SM-88 Used With Methoxsalen, Phenytoin, and Sirolimus (MPS) as Response Maintenance Therapy Following Standard Treatments for Patients With Ewing's Sarcoma or as Salvage Therapy for Patients With Clinically Advanced Sarcomas
Estimated Study Start Date : May 31, 2019
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : May 31, 2022


Arm Intervention/treatment
Experimental: Maintenance Treatment: Ewing's Sarcoma
Combination metyrosine-derivative, low-dose sirolimus, phenytoin and methoxsalen
Drug: Combination metyrosine-derivative, low-dose sirolimus, phenytoin and methoxsalen
Daily oral combination therapy for cancer
Other Name: SM-88

Experimental: Salvage Treatment: Sarcoma
Combination metyrosine-derivative, low-dose sirolimus, phenytoin and methoxsalen
Drug: Combination metyrosine-derivative, low-dose sirolimus, phenytoin and methoxsalen
Daily oral combination therapy for cancer
Other Name: SM-88




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



Information from the National Library of Medicine

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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 30 days prior to enrollment
  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) within 30 days 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03778996


Contacts
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Contact: Sant P Chawla, MD 310-552-9999 santchawla@sarcomaoncology.com

Sponsors and Collaborators
Sarcoma Oncology Research Center, LLC
Joseph Ahmed Foundation
Tyme, Inc
Investigators
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Principal Investigator: Sant P Chawla, MD Sarcoma Oncology Research Center

Additional Information:
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Responsible Party: Sarcoma Oncology Research Center, LLC
ClinicalTrials.gov Identifier: NCT03778996     History of Changes
Other Study ID Numbers: SM-88-JAF-16
First Posted: December 18, 2018    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Phenytoin
Sarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Sirolimus
Everolimus
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
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Photosensitizing Agents
Dermatologic Agents