A Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma

NCT02234986 | Completed Phase 2 Results

• 1 other identifier: 2076-CL-006
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

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.

Conditions

Advanced Adult Hepatocellular Carcinoma; Advanced Fibrolamellar Carcinoma

Keywords

Advanced Fibrolamellar Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  6-month overall response rate (ORR rate) using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR) - disappearance of all target lesions; partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; ORR = proportion of patients evaluated as CR + PR

  6 months

Secondary Outcomes (1)

• Progression Free Survival

  6 months

Other Outcomes (1)

• Frequency and Severity of Adverse Events

  6 months

Study Arms (1)

ENMD-2076

EXPERIMENTAL

ENMD-2076, oral capsule Once daily dose 250 mg/day

Drug: ENMD-2076

Interventions

ENMD-2076 DRUG

250 mg oral dose, once daily (QD) for 28 day cycles

ENMD-2076

Eligibility Criteria

• Age: 12 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Institutional Review Board (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:
• Aspartate aminotransferase (AST) and alanine aminotransferase (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 Eastern Cooperative Oncology Group (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.

You may not qualify if:

• 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.
• Known untreated or unstable central nervous system (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.

Sponsors & Collaborators

• CASI Pharmaceuticals, Inc.: lead

Study Sites (5)

CASI Site 03

San Francisco, California, 94158, United States

Location

CASI Site 04

Aurora, Colorado, 80045, United States

Location

CASI Site 02

Boston, Massachusetts, 01003, United States

Location

Casi Site 01

New York, New York, 10065, United States

Location

CASI Site 05

Dallas, Texas, 75231, United States

Location

Related Publications (1)

• 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.

  PMID: 32154962 DERIVED

MeSH Terms

Interventions

ENMD 2076

Results Point of Contact

• Title: Dr. Alexander Zukiwski
• Organization: CASI Pharmaceuticals, Inc.

alexz@casipharmaceuticals.com

+1 240 864 2888

Study Officials

• Ken Ren, PhD

  CASI Pharmaceuticals, Inc.

  STUDY DIRECTOR

• Ghassan Abou-Alfa, MD

  MSKCC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2014
• First Posted: September 9, 2014
• Study Start: October 1, 2015
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: April 18, 2025
• Results First Posted: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)