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

• ClinicalTrials.gov Identifier: NCT02234986
• Recruitment Status: Completed
• First Posted: September 9, 2014
• Last Update Posted: September 6, 2018
• Sponsor: CASI Pharmaceuticals, Inc.
• Information provided by (Responsible Party): CASI Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: September 5, 2014
• First Posted Date: September 9, 2014
• Last Update Posted Date: September 6, 2018
• Study Start Date: October 2015
• Actual Primary Completion Date: June 30, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 7, 2015)

Overall Response Rate [ Time Frame: 6 months ]

6-month overall response rate (ORR rate) using RECIST v1.1 criteria

Original Primary Outcome Measures (submitted: September 5, 2014)

Progression Free Survival [ Time Frame: 6 months ]

6-month progression free survival (PFS6) rate

Current Secondary Outcome Measures (submitted: October 7, 2015)

Progression Free Survival (PFS6) rate [ Time Frame: 6 months ]

Overall response rate using RECIST v 1.1 criteria

Original Secondary Outcome Measures (submitted: September 5, 2014)

Overall response rate [ Time Frame: 6 months ]

Overall response rate using RECIST v 1.1 criteria

Current Other Pre-specified Outcome Measures (submitted: September 4, 2018)

Frequency and severity of adverse events [ Time Frame: 6 months ]

Frequency and severity of adverse events

Original Other Pre-specified Outcome Measures (submitted: September 5, 2014)

Safety [ Time Frame: 6 months ]

Safety of ENMD-2076 as defined by the frequency and severity of adverse events

Descriptive Information

• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Adult Hepatocellular Carcinoma
• Advanced Fibrolamellar Carcinoma

Intervention

Drug: ENMD-2076

250 mg oral dose, QD for 28 day cycles

Study Arms

Experimental: ENMD-2076

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

Intervention: Drug: ENMD-2076

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 4, 2018): 37
• Original Estimated Enrollment (submitted: September 5, 2014): 53
• Actual Study Completion Date: June 30, 2018
• Actual Primary Completion Date: June 30, 2018 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02234986
• Other Study ID Numbers: 2076-CL-006
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: CASI Pharmaceuticals, Inc.
• Study Sponsor: CASI Pharmaceuticals, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Ken Ren, PhD; CASI Pharmaceuticals, Inc.
• Study Chair: Ghassan Abou-Alfa, MD; MSKCC

• PRS Account: CASI Pharmaceuticals, Inc.
• Verification Date: September 2018