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Efatutazone Dihydrochloride in Treating Patients With Previously Treated Myxoid Liposarcoma That Cannot Be Removed by Surgery

NCT02249949

Description:

This phase II trial studies how well efatutazone dihydrochloride works in treating patients with previously treated myxoid liposarcoma that cannot be removed by surgery. Drugs used in chemotherapy, such as efatutazone dihydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Liposarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study of the Peroxisome Proliferator-Activated Receptor Gamma Agonist, <span class="go-doc-concept go-doc-intervention">Efatutazone</span> vs. <span class="go-doc-concept go-doc-intervention">Placebo</span> in Patients With Previously Treated, Unresectable Myxoid Liposarcoma

Title

  • Brief Title: Study of the Peroxisome Proliferator-Activated Receptor Gamma Agonist, Efatutazone vs. Placebo in Patients With Previously Treated, Unresectable Myxoid Liposarcoma
  • Official Title: A Phase II Randomized, Double-Blinded Study of the Peroxisome Proliferator-Activated Receptor Gamma Agonist, Efatutazone vs. Placebo in Patients With Previously Treated, Unresectable Myxoid Liposarcoma
  • Clinical Trial IDs

    NCT ID: NCT02249949

    ORG ID: A091202

    NCI ID: NCI-2014-01028

    Trial Conditions

    Liposarcoma

    Trial Interventions

    Drug Synonyms Arms
    efatutazone Arm I: efatutazone
    placebo Arm II: placebo

    Trial Purpose

    This is a Phase II trial of efatutazone for patients with advanced, unresectable or
    metastatic myxoid liposarcoma, whose disease has progressed on at least one prior systemic
    therapy. This trial will determine if treatment with efatutazone will result in a
    significant improvement in PFS, confirmed response rate and overall survival compared to
    treatment with placebo, in patients with myxoid liposarcoma. It will also determine if
    treatment with efatutazone will not result in a clinically meaningful increase in adverse
    events compared to treatment with placebo, in patients with myxoid liposarcoma.

    Detailed Description

    This randomized Phase II trial will compare the progression-free survival (PFS) of
    efatutazone vs. placebo in patients with advanced, unresectable, or metastatic myxoid
    liposarcoma who have received at least one prior systemic therapy. The placebo arm was
    selected as the standard of care arm for this trial because there is no standard treatment
    option in this disease. Prior studies have shown that the median PFS is generally 3 months
    or less in either the untreated or ineffectively treated patients with liposarcoma. It is
    hoped that efatutazone can increase the median PFS to at least 6 months. In addition to PFS,
    this trial will also compare the confirmed response rate, overall survival (OS), and adverse
    event rates between efatutazone and placebo.

    Primary Objective:

    To compare the progression-free survival (PFS) between efatutazone and placebo in patients
    with advanced myxoid liposarcoma whose disease has progressed on at least one prior therapy

    Secondary Objective:

    To compare the confirmed response rate, overall survival (OS), and adverse event rates
    between efatutazone and placebo in patients with advanced myxoid liposarcoma whose disease
    has progressed on at least one prior therapy.

    Patients should receive full supportive care while on this study which may include blood
    product support, antibiotic treatment, and treatment of other newly diagnosed or concurrent
    medical conditions. All patients will be unblinded upon disease progression and patients in
    the placebo group will be allowed to cross over to treatment with efatutazone. Treatment
    will continue until disease progression or unacceptable adverse events for patients in the
    efatutazone group. Patients will be followed for up to 5 years after completion of
    treatment.

    Trial Arms

    Name Type Description Interventions
    Arm I: efatutazone Experimental Patients receive efatutazone 0.5 mg twice daily after confirmation of myxoid liposarcoma. Each cycle is 21 days or 3 weeks. If at reimaging there is no evidence of disease progression and the patient is tolerating therapy then the patient will continue to remain on treatment until progression. All patients will be unblinded upon disease progression and patients in the efatutazone group will discontinue treatment. Patients are followed for a maximum of 5 years after study treatment. efatutazone
    Arm II: placebo Placebo Comparator Patients receive placebo twice daily after confirmation of myxoid liposarcoma. Each cycle is 21 days or 3 weeks. If at reimaging there is no evidence of disease progression and the patient is tolerating therapy then the patient will continue to remain on treatment until progression. All patients will be unblinded upon disease progression and patients in the placebo group will be allowed to cross over to treatment with efatutazone. placebo

    Eligibility Criteria

    Pre-Registration Eligibility Criteria:

    Central pathology review submission: Patients must have a formalin-fixed paraffin-embedded
    (FFPE) tumor block OR 1 representative hematoxylin and eosin (H&E) and 20 unstained myxoid
    liposarcoma tissue slides available for submission to central pathology review. This
    review is mandatory prior to registration to confirm eligibility.

    Registration/Randomization Eligibility Criteria:

    1. Measurable disease defined per the protocol

    2. Prior Treatment: Progression on at least one prior systemic chemotherapy for
    advanced, unresectable or metastatic disease. Prior adjuvant or neoadjuvant therapy
    is not included as prior systemic chemotherapy unless treatment occurred within the 6
    months prior to study enrollment.

    - There is no limit to the number of prior lines of treatment a patient has
    received.

    - No treatment with biologic therapy, immunotherapy, chemotherapy, investigational
    agent for malignancy, or radiation 28 days before study registration. No
    treatment with nitrosourea or mitomycin 42 days before study registration.

    - Patients should have resolution of any toxic effects of prior therapy (except
    alopecia) to National Cancer Institute Common Terminology Criteria for Adverse
    Events (NCI CTCAE), Version 4.0, grade 1 or less.

    3. Disease progression prior to enrollment, defined as a growth in the sum of the
    greatest diameter of the index lesions by at least 20% as per Response Evaluation
    Criteria in Solid Tumors (RECIST) version 1.1 over a period of 6 months or less.

    4. No history of the following:

    - Class III or IV congestive heart failure (CHF)

    - Grade 3 or 4 thromboembolic event 6 months

    - Pericardial effusion 12 months (any grade)

    - Pericardial involvement with tumor

    - Grade 2 or higher pleural effusion 6 months

    5. No symptomatic, untreated, or uncontrolled brain metastases present

    6. Not pregnant and not nursing, because this study involves an investigational agent
    whose genotoxic, mutagenic and teratogenic effects on the developing fetus and
    newborn are unknown.

    - Therefore, for women of childbearing potential only, a negative pregnancy test
    done 7 days prior to registration is required.

    - A female of childbearing potential is a sexually mature female who:

    1. has not undergone a hysterectomy or bilateral oophorectomy or

    2. has not been naturally postmenopausal for at least 12 consecutive months
    (i.e., has had menses at any time in the preceding 12 consecutive months).

    7. Concomitant medications:

    - Patients with diabetes mellitus requiring concurrent treatment with insulin or
    thiazolidinedione (TZD) oral agents are not eligible

    - Patients with known hypersensitivity to any TZD oral agents are not eligible

    8. Age 18 years

    9. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

    10. Required Initial Laboratory Values:

    - Absolute Neutrophil Count (ANC) 1,000/mm^3

    - Platelet Count 75,000/mm^3

    - Creatinine 1.5 mg/dL x upper limits of normal (ULN) or

    - Calc. Creatinine Clearance 30 mL/min

    - Bilirubin 1.5 x ULN

    - SGOT (AST) and SGPT (ALT) 2.5 x ULN *

    - For subjects with liver metastases, serum glutamic oxaloacetic transaminase
    [SGOT] aspartate aminotransferase (AST) and serum glutamic pyruvic
    transaminase [SGPT] alanine transaminase (ALT) < 5 X ULN of institution's
    normal range and bilirubin 3 x ULN are allowed

    11. Documentation of Disease: Histologic Documentation - Eligible patients must have
    histopathologically confirmed myxoid liposarcoma with confirmation of DDIT3
    rearrangement.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression Free Survival

    Secondary Outcome Measures

    Confirmed response rate

    Overall survival

    Frequency and percentage of adverse events of grade 3+ according to Common Terminology Criteria for Adverse Events

    Trial Keywords