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.
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
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
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
- 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
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both