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

Advanced Adult Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase 2, Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma (FLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02234986
• Other study ID #: 2076-CL-006
• Status: Completed
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: June 30, 2018

Study information

• Verified date: September 2018
• Source: CASI Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: June 30, 2018
• Est. primary completion date: June 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Adult Hepatocellular Carcinoma
• Advanced Fibrolamellar Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• ENMD-2076
250 mg oral dose, QD for 28 day cycles

Locations

Country	Name	City	State
United States	CASI Site 04	Aurora	Colorado
United States	CASI Site 02	Boston	Massachusetts
United States	CASI Site 05	Dallas	Texas
United States	Casi Site 01	New York	New York
United States	CASI Site 03	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
CASI Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency and severity of adverse events	Frequency and severity of adverse events	6 months
Primary	Overall Response Rate	6-month overall response rate (ORR rate) using RECIST v1.1 criteria	6 months
Secondary	Progression Free Survival (PFS6) rate	Overall response rate using RECIST v 1.1 criteria	6 months