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

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Liposarcoma
• Intervention: Drug: efatutazone
• Enrollment: 15

Participant Flow

Recruitment Details
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.

Arm/Group Title	Efatutazone Dihydrochloride
Arm/Group Description	Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started	13
Completed	11
Not Completed	2
Reason Not Completed
Cancelled prior to treatment	2

Baseline Characteristics

Arm/Group Title		Efatutazone Dihydrochloride
Arm/Group Description		Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants		11
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	11 participants
		51.4 (17.2)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	Female	4 36.4%
	Male	7 63.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	Hispanic or Latino	2 18.2%
	Not Hispanic or Latino	9 81.8%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	1 9.1%
	White	8 72.7%
	More than one race	0 0.0%
	Unknown or Not Reported	2 18.2%
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants
	0	6 54.5%
	1	5 45.5%
		[1] Measure Description: Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.

Outcome Measures

1. Primary Outcome

Title	Confirmed Overall Response Rate Per the RECIST 1.1 Criteria
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Efatutazone Dihydrochloride
Arm/Group Description:	Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	11
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	0; (0 to 28)

2. Secondary Outcome

Title	Progression Free Survival (PFS) Determined Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Efatutazone Dihydrochloride
Arm/Group Description:	Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	11
Median (95% Confidence Interval); Unit of Measure: months
	1.4 [1]; (1.2 to NA)

[1]

The 95% confidence interval upper limit was not obtained.

3. Secondary Outcome

Title	Overall Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Efatutazone Dihydrochloride
Arm/Group Description:	Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	11
Median (95% Confidence Interval); Unit of Measure: months
	8.6 [1]; (6.8 to NA)

[1]

The 95% confidence interval upper limit was not obtained.

4. Secondary Outcome

Title	Incidence of Grade 3+ Adverse Events Summarized Using Common Terminology Criteria for Adverse Events Version 4.0
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Efatutazone Dihydrochloride
Arm/Group Description:	Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed	11
Measure Type: Count of Participants; Unit of Measure: Participants
at least one grade 3 or worse AE	6 54.5%
at least one grade 4 or worse AE	3 27.3%

Adverse Events

Time Frame	Adverse events are assessed weekly during cycle 1, and then on day 1 (+/- 4 days) for cycles 2-4; then day 1 (+/- 7 days) of every odd numbered cycle for Cycle 5 and beyond; up to 5 years.
Adverse Event Reporting Description	Each CTCAE term is a representation of a specific event used for medical documentation & analysis & is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for completed patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, & appear in the SAE table.
Arm/Group Title	Efatutazone Dihydrochloride
Arm/Group Description	Patients receive efatutazone dihydrochloride PO BID continuously. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
	Efatutazone Dihydrochloride
	Affected / at Risk (%)
Total	8/11 (72.73%)
Serious Adverse Events
	Efatutazone Dihydrochloride
	Affected / at Risk (%)	# Events
Total	6/11 (54.55%)
Blood and lymphatic system disorders
Anemia † 1	3/11 (27.27%)	4
Gastrointestinal disorders
Abdominal pain † 1	1/11 (9.09%)	1
Gastrointestinal disorders - Other, specify † 1	1/11 (9.09%)	1
Small intestinal perforation † 1	1/11 (9.09%)	1
General disorders
Edema limbs † 1	1/11 (9.09%)	1
Edema trunk † 1	1/11 (9.09%)	1
Fever † 1	1/11 (9.09%)	1
Infections and infestations
Abdominal infection † 1	1/11 (9.09%)	1
Bronchial infection † 1	1/11 (9.09%)	1
Investigations
Neutrophil count decreased † 1	1/11 (9.09%)	2
Platelet count decreased † 1	1/11 (9.09%)	2
Musculoskeletal and connective tissue disorders
Back pain † 1	2/11 (18.18%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1	1/11 (9.09%)	1
Tumor pain † 1	1/11 (9.09%)	1
1 Term from vocabulary, MedDRA 12; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Efatutazone Dihydrochloride
	Affected / at Risk (%)	# Events
Total	11/11 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	6/11 (54.55%)	19
Blood and lymphatic system disorders - Other, specify † 1	1/11 (9.09%)	1
Gastrointestinal disorders
Constipation † 1	1/11 (9.09%)	1
Diarrhea † 1	1/11 (9.09%)	1
Nausea † 1	3/11 (27.27%)	4
Vomiting † 1	1/11 (9.09%)	1
General disorders
Edema face † 1	1/11 (9.09%)	2
Edema limbs † 1	8/11 (72.73%)	26
Edema trunk † 1	1/11 (9.09%)	1
Fatigue † 1	7/11 (63.64%)	21
Investigations
Cholesterol high † 1	1/11 (9.09%)	2
Creatinine increased † 1	2/11 (18.18%)	2
Lymphocyte count decreased † 1	2/11 (18.18%)	5
Neutrophil count decreased † 1	1/11 (9.09%)	1
Weight gain † 1	8/11 (72.73%)	23
White blood cell decreased † 1	2/11 (18.18%)	2
Metabolism and nutrition disorders
Anorexia † 1	2/11 (18.18%)	3
Dehydration † 1	1/11 (9.09%)	1
Hypertriglyceridemia † 1	2/11 (18.18%)	4
Hyponatremia † 1	1/11 (9.09%)	1
Musculoskeletal and connective tissue disorders
Back pain † 1	1/11 (9.09%)	1
Buttock pain † 1	1/11 (9.09%)	1
Generalized muscle weakness † 1	1/11 (9.09%)	1
Muscle weakness lower limb † 1	1/11 (9.09%)	1
Pain in extremity † 1	1/11 (9.09%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain † 1	1/11 (9.09%)	1
Nervous system disorders
Dizziness † 1	1/11 (9.09%)	2
Dysgeusia † 1	1/11 (9.09%)	2
Headache † 1	1/11 (9.09%)	1
Psychiatric disorders
Insomnia † 1	1/11 (9.09%)	4
Reproductive system and breast disorders
Genital edema † 1	1/11 (9.09%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/11 (9.09%)	1
Dyspnea † 1	1/11 (9.09%)	1
Pleural effusion † 1	2/11 (18.18%)	3
Skin and subcutaneous tissue disorders
Periorbital edema † 1	1/11 (9.09%)	1
Rash maculo-papular † 1	1/11 (9.09%)	1
Skin and subcutaneous tissue disorders - Other, specify † 1	1/11 (9.09%)	2
Vascular disorders
Hypertension † 1	2/11 (18.18%)	2
1 Term from vocabulary, MedDRA 12; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Michael J. Pishvaian, MD, PhD
• Organization: Georgetown University
• Phone: 202-444-2144
• EMail: pishvaim@georgetown.edu

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT02249949
• Other Study ID Numbers: A091202; NCI-2014-01028 ( Registry Identifier: NCI Clinical Trials Reporting Program )
• First Submitted: September 24, 2014
• First Posted: September 26, 2014
• Results First Submitted: June 10, 2019
• Results First Posted: June 27, 2019
• Last Update Posted: July 24, 2020