A Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma
Primary Purpose
Advanced Adult Hepatocellular Carcinoma, Advanced Fibrolamellar Carcinoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ENMD-2076
Sponsored by

About this trial
This is an interventional treatment trial for Advanced Adult Hepatocellular Carcinoma focused on measuring Advanced Fibrolamellar Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed advanced fibrolamellar carcinoma (FLC).
- All forms of prior local therapy are allowed as long as patients have either a target lesion, which has not been treated with local therapy and/or the target lesion(s) within the field of the local-regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy.
- Are at least 4 weeks from major surgery and recovered.
- At least one measureable lesion by RECIST 1.1.
- Male or non-pregnant, non-breastfeeding female at least 18 years of age. Patients aged at 12~18 years may be recruited but only at the site principle investigator's request and subject to IRB approval.
- Has a pre-study echocardiogram or multi-gated acquisition (MUGA) scan with an actual left ventricular ejection fraction of greater than or equal to the institutional lower limit of normal within one month of initiating therapy.
Have clinically acceptable laboratory screening results within certain limits specified below:
- AST and ALT ≤ 5 times upper limit of normal (ULN)
- Total bilirubin ≤ 3.0 x ULN
- Creatinine ≤ 1.5 x ULN or Cr Cl > 60 cc/min
- Absolute neutrophil count ≥ 1500 cells/mm3
- Platelets ≥ 50,000/mm3
- Have an ECOG performance status of 0-2 for ≥ 16 years of age and a Lansky performance status of 70-100 for < 16 years of age
- Women and men of child producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential.
- Have the ability to understand the requirements of the study, provide written informed consent, which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments.
Exclusion Criteria:
- Have active, acute, or chronic clinically significant infections or bleeding within the last 6 months or previous thromboembolic or hemorrhagic events during anti angiogenic therapy.
- Have uncontrolled hypertension (systolic blood pressure greater than 150 or diastolic blood pressure greater than 100) or history of congestive heart failure (AHA Grade 2 or higher).
- Have active angina pectoris, stroke or recent myocardial infarction (within 6 months).
- Have uncontrolled chronic atrial fibrillation.
- Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec in adults and 450 msec in pediatrics (< 18 years).
- Have additional uncontrolled serious medical or psychiatric illness that in the point of view of the investigator can render the patient unable to receive therapy or make it unsafe to receive therapy.
- Require treatment with any of the exclusionary medications listed in Appendix D.
- Known untreated or unstable CNS metastatic disease.
- Have persistent 2+ protein by urinalysis (patients with 2+ proteinuria that have a spot protein:creatinine ratio of less than 0.3 may be enrolled) or a history of nephrotic syndrome.
- Subjects with history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the investigator will not affect patient outcome in the setting of current FLC diagnosis.
Sites / Locations
- CASI Site 03
- CASI Site 04
- CASI Site 02
- Casi Site 01
- CASI Site 05
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ENMD-2076
Arm Description
ENMD-2076, oral capsule Once daily dose 250 mg/day
Outcomes
Primary Outcome Measures
Overall Response Rate
6-month overall response rate (ORR rate) using RECIST v1.1 criteria
Secondary Outcome Measures
Progression Free Survival (PFS6) rate
Overall response rate using RECIST v 1.1 criteria
Full Information
NCT ID
NCT02234986
First Posted
September 5, 2014
Last Updated
September 4, 2018
Sponsor
CASI Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02234986
Brief Title
A Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma
Official Title
A Phase 2, Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma (FLC)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
October 2015 (undefined)
Primary Completion Date
June 30, 2018 (Actual)
Study Completion Date
June 30, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CASI Pharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of the study is to determine whether once-daily dosing with ENMD-2076 will be a safe and effective treatment in patients with FLC. Safety will be measured by looking at the adverse events that may happen and the efficacy will look at the progression of the disease over time.
Detailed Description
Primary Objective:
• To determine the 6-month progression free survival (PFS6) rate when patients with advanced fibrolamellar carcinoma (FLC) are treated with daily oral ENMD 2076
Secondary Objectives:
To evaluate the overall response rate using RECIST v 1.1 criteria when patients with FLC are treated with daily oral ENMD 2076.
To evaluate the median Progression Free Survival (PFS), Time to Progression (TTP), and Overall Survival (OS).
To determine the safety of ENMD-2076 as defined by the frequency and severity of adverse events when patients with FLC are treated with daily oral ENMD-2076
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Adult Hepatocellular Carcinoma, Advanced Fibrolamellar Carcinoma
Keywords
Advanced Fibrolamellar Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ENMD-2076
Arm Type
Experimental
Arm Description
ENMD-2076, oral capsule Once daily dose 250 mg/day
Intervention Type
Drug
Intervention Name(s)
ENMD-2076
Intervention Description
250 mg oral dose, QD for 28 day cycles
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
6-month overall response rate (ORR rate) using RECIST v1.1 criteria
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS6) rate
Description
Overall response rate using RECIST v 1.1 criteria
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Frequency and severity of adverse events
Description
Frequency and severity of adverse events
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically confirmed advanced fibrolamellar carcinoma (FLC).
All forms of prior local therapy are allowed as long as patients have either a target lesion, which has not been treated with local therapy and/or the target lesion(s) within the field of the local-regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy.
Are at least 4 weeks from major surgery and recovered.
At least one measureable lesion by RECIST 1.1.
Male or non-pregnant, non-breastfeeding female at least 18 years of age. Patients aged at 12~18 years may be recruited but only at the site principle investigator's request and subject to IRB approval.
Has a pre-study echocardiogram or multi-gated acquisition (MUGA) scan with an actual left ventricular ejection fraction of greater than or equal to the institutional lower limit of normal within one month of initiating therapy.
Have clinically acceptable laboratory screening results within certain limits specified below:
AST and ALT ≤ 5 times upper limit of normal (ULN)
Total bilirubin ≤ 3.0 x ULN
Creatinine ≤ 1.5 x ULN or Cr Cl > 60 cc/min
Absolute neutrophil count ≥ 1500 cells/mm3
Platelets ≥ 50,000/mm3
Have an ECOG performance status of 0-2 for ≥ 16 years of age and a Lansky performance status of 70-100 for < 16 years of age
Women and men of child producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential.
Have the ability to understand the requirements of the study, provide written informed consent, which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments.
Exclusion Criteria:
Have active, acute, or chronic clinically significant infections or bleeding within the last 6 months or previous thromboembolic or hemorrhagic events during anti angiogenic therapy.
Have uncontrolled hypertension (systolic blood pressure greater than 150 or diastolic blood pressure greater than 100) or history of congestive heart failure (AHA Grade 2 or higher).
Have active angina pectoris, stroke or recent myocardial infarction (within 6 months).
Have uncontrolled chronic atrial fibrillation.
Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec in adults and 450 msec in pediatrics (< 18 years).
Have additional uncontrolled serious medical or psychiatric illness that in the point of view of the investigator can render the patient unable to receive therapy or make it unsafe to receive therapy.
Require treatment with any of the exclusionary medications listed in Appendix D.
Known untreated or unstable CNS metastatic disease.
Have persistent 2+ protein by urinalysis (patients with 2+ proteinuria that have a spot protein:creatinine ratio of less than 0.3 may be enrolled) or a history of nephrotic syndrome.
Subjects with history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the investigator will not affect patient outcome in the setting of current FLC diagnosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ken Ren, PhD
Organizational Affiliation
CASI Pharmaceuticals, Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Ghassan Abou-Alfa, MD
Organizational Affiliation
MSKCC
Official's Role
Study Chair
Facility Information:
Facility Name
CASI Site 03
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
CASI Site 04
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
CASI Site 02
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
01003
Country
United States
Facility Name
Casi Site 01
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
CASI Site 05
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
32154962
Citation
Abou-Alfa GK, Mayer R, Venook AP, O'Neill AF, Beg MS, LaQuaglia M, Kingham PT, Kobos R, Basturk O, Brennan C, Yopp A, Harding JJ, Leong S, Crown J, Hoti E, Leonard G, Ly M, Bradley M, Valentino E, Markowitz D, Zukiwski A, Ren K, Gordan JD. Phase II Multicenter, Open-Label Study of Oral ENMD-2076 for the Treatment of Patients with Advanced Fibrolamellar Carcinoma. Oncologist. 2020 Dec;25(12):e1837-e1845. doi: 10.1634/theoncologist.2020-0093. Epub 2020 Mar 10.
Results Reference
derived
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A Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma
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