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

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)

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
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall Response Rate

Secondary Outcome

 Progression Free Survival (PFS6) rate

Condition

Advanced Adult Hepatocellular Carcinoma

Intervention

ENMD-2076

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

37

Start Date

October 2015

Completion Date

June 30, 2018

Primary Completion Date

June 30, 2018

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.
      

Gender

All

Ages

18 Years - 99 Years

Accepts Healthy Volunteers

No

Contacts

Ken Ren, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02234986

Organization ID

2076-CL-006


Responsible Party

Sponsor

Study Sponsor

CASI Pharmaceuticals, Inc.


Study Sponsor

Ken Ren, PhD, Study Director, CASI Pharmaceuticals, Inc.


Verification Date

September 2018