Liposarcoma
Conditions
Brief summary
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.
Detailed description
PRIMARY OBJECTIVES: I. To determine the confirmed response rate for efatutazone dihydrochloride (efatutazone) in patients with advanced myxoid liposarcoma whose disease has progressed on at least one prior therapy. SECONDARY OBJECTIVES: I. To assess the progression free survival (PFS), overall survival (OS), and adverse event rates for efatutazone treated patients with advanced myxoid liposarcoma whose disease has progressed on at least one prior therapy. TERTIARY OBJECTIVES: I. To assess the predictive value of peroxisome proliferator-activated receptor (PPAR) and retinoid X receptors (RXR) tumor expression from archived patient tumor samples. II. To assess the predictive value of the expression of PPARgamma-regulated markers of adipocytes differentiation. III. To assess the predictive value of the expression of PPARgamma-regulated cell cycle proteins. IV. To assess the effects of efatutazone treatment on serum adiponectin levels. OUTLINE: Patients receive efatutazone dihydrochloride orally (PO) twice daily (BID) continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks for 2 years and then every 6 months for up to 5 years.
Interventions
DRUGefatutazone
Given PO
Sponsors
National Cancer Institute (NCI)
Daiichi Sankyo
Alliance for Clinical Trials in Oncology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * Measurable disease * 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 (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, grade 1 or less * No history of the following: * Class III or IV congestive heart failure (CHF) * Pericardial effusion =\< 12 months (grade 3 or 4) * Pericardial involvement with tumor * Grade 2 or higher pleural effusion =\< 6 months * No symptomatic, untreated, or uncontrolled brain metastases present * Not pregnant and not nursing; 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: * Has not undergone a hysterectomy or bilateral oophorectomy; or * 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) * 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 * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * 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 calculated (calc.) creatinine clearance \>= 30 mL/min * Bilirubin =\< 1.5 x ULN; for subjects with liver metastases =\< 3 x ULN is allowed * Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 2.5 x ULN; for subjects with liver metastases, SGOT (AST) and SGPT (ALT) \< 5 x the upper normal limit of institution's normal range is allowed * Eligible patients must have histopathologically confirmed myxoid liposarcoma with confirmation of DDIT3 rearrangement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Overall Response Rate Per the RECIST 1.1 Criteria | Up to 24 weeks (8 cycles) | The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Determined Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Time from study entry to the first of either disease progression or death from any cause, assessed up to 5 years | Progression free survival (PFS) is defined as the time from study entry to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. |
| Overall Survival | Time from study entry to death from any cause, assessed up to 5 years | Overall survival time is defined as the time from study entry to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. |
| Incidence of Grade 3+ Adverse Events Summarized Using Common Terminology Criteria for Adverse Events Version 4.0 | Up to 5 years | Incidence of grade 3+ adverse events summarized using Common Terminology Criteria for Adverse Events version 4.0: The frequency and percentage of grade 3+ adverse events will be estimated |
Countries
United States
Participant flow
Pre-assignment details
A protocol amendment (Update #02) removed the option for patients to be randomized to Placebo; the study went from being a randomized study to a single arm study. The discrepancy in the number of patients who 'Started' the study and the Protocol Enrollment number is due to there being 2 patients randomized to Placebo prior to Update #02.
Participants by arm
| Arm | Count |
|---|---|
| Efatutazone Dihydrochloride Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Cancelled prior to treatment | 2 |
Baseline characteristics
| Characteristic | Efatutazone Dihydrochloride |
|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 17.2 |
| ECOG Performance Status 0 | 6 Participants |
| ECOG Performance Status 1 | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 6 / 11 |
Outcome results
Primary
Confirmed Overall Response Rate Per the RECIST 1.1 Criteria
The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients.
Time frame: Up to 24 weeks (8 cycles)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Efatutazone Dihydrochloride | Confirmed Overall Response Rate Per the RECIST 1.1 Criteria | 0 percentage of patients |
Secondary
Incidence of Grade 3+ Adverse Events Summarized Using Common Terminology Criteria for Adverse Events Version 4.0
Incidence of grade 3+ adverse events summarized using Common Terminology Criteria for Adverse Events version 4.0: The frequency and percentage of grade 3+ adverse events will be estimated
Time frame: Up to 5 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Efatutazone Dihydrochloride | Incidence of Grade 3+ Adverse Events Summarized Using Common Terminology Criteria for Adverse Events Version 4.0 | at least one grade 3 or worse AE | 6 Participants |
| Efatutazone Dihydrochloride | Incidence of Grade 3+ Adverse Events Summarized Using Common Terminology Criteria for Adverse Events Version 4.0 | at least one grade 4 or worse AE | 3 Participants |
Secondary
Overall Survival
Overall survival time is defined as the time from study entry to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time frame: Time from study entry to death from any cause, assessed up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efatutazone Dihydrochloride | Overall Survival | 8.6 months |
Secondary
Progression Free Survival (PFS) Determined Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Progression free survival (PFS) is defined as the time from study entry to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time frame: Time from study entry to the first of either disease progression or death from any cause, assessed up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efatutazone Dihydrochloride | Progression Free Survival (PFS) Determined Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 1.4 months |