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

A Phase II Study of the Peroxisome Proliferator-Activated Receptor Gamma Agonist, Efatutazone in Patients With Previously Treated, Unresectable Myxoid Liposarcoma

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.

Study Overview

• Status: Completed
• Conditions: Liposarcoma
• Intervention / Treatment: Drug: efatutazone

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Cumming, Georgia, United States, 30041
      • Northside Hospital-Forsyth
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • 'Aiea, Hawaii, United States, 96701
      • The Cancer Center of Hawaii-Pali Momi
    • 'Aiea, Hawaii, United States, 96701
      • Hawaii Oncology Inc-Pali Momi
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Cancer Care Inc-Liliha
    • Honolulu, Hawaii, United States, 96817
      • Kuakini Medical Center
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • Island Urology
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc-POB II
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Oncology Inc-POB I
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Oncology Inc-Kuakini
    • Lihue, Hawaii, United States, 96766
      • Wilcox Memorial Hospital and Kauai Medical Clinic
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carbondale, Illinois, United States, 62902
      • Memorial Hospital of Carbondale
    • Carterville, Illinois, United States, 62918
      • SIH Cancer Institute
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Danville, Illinois, United States, 61832
      • Carle on Vermilion
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Central Illinois
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Radiation Oncology of Northern Illinois
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Springfield, Illinois, United States, 62702
      • Central Illinois Hematology Oncology Center
    • Swansea, Illinois, United States, 62226
      • Cancer Care Specialists of Illinois-Swansea
    • Swansea, Illinois, United States, 62226
      • Memorial and Saint Elizabeth's Health Care Services LLP
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Yorkville, Illinois, United States, 60560
      • Rush-Copley Healthcare Center
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Deaconess Clinic Downtown
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • Michigan City, Indiana, United States, 46360
      • Woodland Cancer Care Center
    • Newburgh, Indiana, United States, 47630
      • Chancellor Center for Oncology
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Kansas Institute of Medicine Cancer and Blood Center
    • Lenexa, Kansas, United States, 66219
      • Minimally Invasive Surgery Hospital
    • Overland Park, Kansas, United States, 66209
      • Menorah Medical Center
    • Overland Park, Kansas, United States, 66213
      • Saint Luke's South Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
  • Missouri
    • Ballwin, Missouri, United States, 63011
      • Saint Louis Cancer and Breast Institute-Ballwin
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Branson, Missouri, United States, 65616
      • Cox Cancer Center Branson
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Independence, Missouri, United States, 64057
      • Centerpoint Medical Center LLC
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital of Kansas City
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
    • Lee's Summit, Missouri, United States, 64086
      • Saint Luke's East - Lee's Summit
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Saint Joseph, Missouri, United States, 64507
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • Missouri Baptist Outpatient Center-Sunset Hills
    • Washington, Missouri, United States, 63090
      • Mercy Hospital Washington
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
    • Manchester, New Hampshire, United States, 03102
      • Norris Cotton Cancer Center-Manchester
    • Nashua, New Hampshire, United States, 03063
      • Norris Cotton Cancer Center-Nashua
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Columbia University/Herbert Irving Cancer Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Hospital Oklahoma City
    • Oklahoma City, Oklahoma, United States, 73109
      • Integris Southwest Medical Center
    • Oklahoma City, Oklahoma, United States, 73142
      • Integris Cancer Institute of Oklahoma
  • South Carolina
    • Easley, South Carolina, United States, 29640
      • Greenville Health System Cancer Institute-Easley
    • Greenville, South Carolina, United States, 29601
      • Greenville Health System Cancer Institute-Andrews
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29605
      • Greenville Memorial Hospital
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Butternut
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • Vermont
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center-North
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: efatutazone dihydrochloride; Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: efatutazone; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 24 weeks (8 cycles)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 from study entry to the first of either disease progression or death from any cause, assessed up to 5 years
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 from study entry to death from any cause, assessed up to 5 years
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	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI); Daiichi Sankyo, Inc.
• Investigators: Study Chair: Michael Pishvaian, MD, PhD, Georgetown University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): October 4, 2018
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: September 24, 2014
• First Submitted That Met QC Criteria: September 25, 2014
• First Posted (Estimated): September 26, 2014

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Adipose Tissue; Liposarcoma; Liposarcoma, Myxoid; Antineoplastic Agents; Efatutazone
• Other Study ID Numbers: A091202; NCI-2014-01028 (Registry Identifier: NCI Clinical Trials Reporting Program)