Clinical trial NCT02249949: Efatutazone Dihydrochloride in Treating Patients With Previously Treated Myxoid Liposarcoma That Cannot Be Removed by Surgery
Official title: A Phase II Study of the Peroxisome Proliferator-Activated Receptor Gamma Agonist, Efatutazone in Patients With Previously Treated, Unresectable Myxoid Liposarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liposarcoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Daiichi Sankyo
First posted: 2014-09-26
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Confirmed Overall Response Rate Per the RECIST 1.1 Criteria
timeFrame: Up to 24 weeks (8 cycles)
Secondary outcomes:
measure: Progression Free Survival (PFS) Determined Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Time from study entry to the first of either disease progression or death from any cause, assessed up to 5 years
measure: Overall Survival
timeFrame: Time from study entry to death from any cause, assessed up to 5 years
measure: Incidence of Grade 3+ Adverse Events Summarized Using Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Cumming
country: United States
facility: Northside Hospital-Forsyth
state: Georgia
city: 'Aiea
country: United States
facility: Hawaii Oncology Inc-Pali Momi
state: Hawaii
city: 'Aiea
country: United States
facility: Pali Momi Medical Center
state: Hawaii
city: 'Aiea
country: United States
facility: The Cancer Center of Hawaii-Pali Momi
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Cancer Care Inc-POB II
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Oncology Inc-POB I
state: Hawaii
city: Honolulu
country: United States
facility: Island Urology
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital
state: Hawaii
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Cancer Care Inc-Liliha
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Oncology Inc-Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: Kuakini Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: The Cancer Center of Hawaii-Liliha
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Lihue
country: United States
facility: Wilcox Memorial Hospital and Kauai Medical Clinic
state: Hawaii
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Illinois CancerCare-Bloomington
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare-Canton
state: Illinois
city: Carbondale
country: United States
facility: Memorial Hospital of Carbondale
state: Illinois
city: Carterville
country: United States
facility: SIH Cancer Institute
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare-Carthage
state: Illinois
city: Centralia
country: United States
facility: Centralia Oncology Clinic
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Danville
country: United States
facility: Carle on Vermilion
state: Illinois
city: Decatur
country: United States
facility: Cancer Care Specialists of Central Illinois
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Effingham
country: United States
facility: Carle Physician Group-Effingham
state: Illinois
city: Effingham
country: United States
facility: Crossroads Cancer Center
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare-Eureka
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare-Galesburg
state: Illinois
city: Galesburg
country: United States
facility: Western Illinois Cancer Treatment Center
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare-Kewanee Clinic
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare-Macomb
state: Illinois
city: Mattoon
country: United States
facility: Carle Physician Group-Mattoon/Charleston
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Mount Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Ottawa
country: United States
facility: Radiation Oncology of Northern Illinois
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare-Pekin
state: Illinois
city: Pekin
country: United States
facility: OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Radiation Oncology at Peoria Cancer Center
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare-Peru
state: Illinois
city: Peru
country: United States
facility: Valley Radiation Oncology
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare-Princeton
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Springfield
country: United States
facility: Memorial Medical Center
state: Illinois
city: Swansea
country: United States
facility: Cancer Care Specialists of Illinois-Swansea
state: Illinois
city: Swansea
country: United States
facility: Memorial and Saint Elizabeth's Health Care Services LLP
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Urbana
country: United States
facility: The Carle Foundation Hospital
state: Illinois
city: Yorkville
country: United States
facility: Rush-Copley Healthcare Center
state: Illinois
city: Evansville
country: United States
facility: Deaconess Clinic Downtown
state: Indiana
city: Michigan City
country: United States
facility: Franciscan Saint Anthony Health-Michigan City
state: Indiana
city: Michigan City
country: United States
facility: Woodland Cancer Care Center
state: Indiana
city: Newburgh
country: United States
facility: Chancellor Center for Oncology
state: Indiana
city: Lenexa
country: United States
facility: Kansas Institute of Medicine Cancer and Blood Center
state: Kansas
city: Lenexa
country: United States
facility: Minimally Invasive Surgery Hospital
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Saint Luke's South Hospital
state: Kansas
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Ballwin
country: United States
facility: Saint Louis Cancer and Breast Institute-Ballwin
state: Missouri
city: Bolivar
country: United States
facility: Central Care Cancer Center - Bolivar
state: Missouri
city: Bonne Terre
country: United States
facility: Parkland Health Center-Bonne Terre
state: Missouri
city: Branson
country: United States
facility: Cox Cancer Center Branson
state: Missouri
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Cape Girardeau
country: United States
facility: Southeast Cancer Center
state: Missouri
city: Creve Coeur
country: United States
facility: Siteman Cancer Center at West County Hospital
state: Missouri
city: Independence
country: United States
facility: Centerpoint Medical Center LLC
state: Missouri
city: Jefferson City
country: United States
facility: Capital Region Southwest Campus
state: Missouri
city: Joplin
country: United States
facility: Freeman Health System
state: Missouri
city: Joplin
country: United States
facility: Mercy Hospital Joplin
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Lee's Summit
country: United States
facility: Saint Luke's East - Lee's Summit
state: Missouri
city: Rolla
country: United States
facility: Delbert Day Cancer Institute at PCRMC
state: Missouri
city: Rolla
country: United States
facility: Mercy Clinic-Rolla-Cancer and Hematology
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis Cancer and Breast Institute-South City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center-South County
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Sainte Genevieve
country: United States
facility: Sainte Genevieve County Memorial Hospital
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Sullivan
country: United States
facility: Missouri Baptist Sullivan Hospital
state: Missouri
city: Sunset Hills
country: United States
facility: Missouri Baptist Outpatient Center-Sunset Hills
state: Missouri
city: Washington
country: United States
facility: Mercy Hospital Washington
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Manchester
country: United States
facility: Norris Cotton Cancer Center-Manchester
state: New Hampshire
city: Nashua
country: United States
facility: Norris Cotton Cancer Center-Nashua
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University/Herbert Irving Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Oklahoma City
country: United States
facility: Integris Southwest Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Mercy Hospital Oklahoma City
state: Oklahoma
city: Oklahoma City
country: United States
facility: Integris Cancer Institute of Oklahoma
state: Oklahoma
city: Easley
country: United States
facility: Greenville Health System Cancer Institute-Easley
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Andrews
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Butternut
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Faris
state: South Carolina
city: Greenville
country: United States
facility: Greenville Memorial Hospital
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute-Eastside
state: South Carolina
city: Greer
country: United States
facility: Greenville Health System Cancer Institute-Greer
state: South Carolina
city: Seneca
country: United States
facility: Greenville Health System Cancer Institute-Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: Greenville Health System Cancer Institute-Spartanburg
state: South Carolina
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center-North
state: Vermont
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Georgetown University
name: Michael Pishvaian, MD, PhD
role: STUDY_CHAIR
References: