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

• ClinicalTrials.gov Identifier: NCT02249949
• Recruitment Status: Active, not recruiting
• First Posted: September 26, 2014
• Results First Posted: June 27, 2019
• Last Update Posted: July 24, 2020
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI); Daiichi Sankyo, Inc.
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

Tracking Information

• First Submitted Date: September 24, 2014
• First Posted Date: September 26, 2014
• Results First Submitted Date: June 10, 2019
• Results First Posted Date: June 27, 2019
• Last Update Posted Date: July 24, 2020
• Actual Study Start Date: October 2014
• Actual Primary Completion Date: October 4, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 10, 2019)

Confirmed Overall Response Rate Per the RECIST 1.1 Criteria [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: September 25, 2014): Progression Free Survival [ Time Frame: 5 years post-study treatment ]

Current Secondary Outcome Measures (submitted: June 10, 2019)

• Progression Free Survival (PFS) Determined Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: 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 Frame: 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 [ Time Frame: 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

Original Secondary Outcome Measures (submitted: September 25, 2014)

• Confirmed response rate [ Time Frame: Up to 5 years post-study treatment ]
• Overall Survival [ Time Frame: Up to 5 years post-study treatment ]
• Frequency and percentage of adverse events of grade 3+ according to Common Terminology Criteria for Adverse Events [ Time Frame: Up to 5 years post-study treatment ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Liposarcoma

Intervention

Drug: efatutazone

Given PO

Study Arms

Experimental: efatutazone dihydrochloride

Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Intervention: Drug: efatutazone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 8, 2018): 15
• Original Estimated Enrollment (submitted: September 25, 2014): 36
• Study Completion Date: Not Provided
• Actual Primary Completion Date: October 4, 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02249949
• Other Study ID Numbers: A091202; NCI-2014-01028 ( Registry Identifier: NCI Clinical Trials Reporting Program )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Alliance for Clinical Trials in Oncology
• Study Sponsor: Alliance for Clinical Trials in Oncology

Collaborators

• National Cancer Institute (NCI)
• Daiichi Sankyo, Inc.

Investigators

• Study Chair: Michael Pishvaian, MD, PhD; Georgetown University

• PRS Account: Alliance for Clinical Trials in Oncology
• Verification Date: July 2020