LEE001 and Chemoembolization In Patients With Advanced Hepatocellular Carcinoma

NCT02524119 | Terminated Phase 2 Results DMC

• 1 other identifier: STU 052015-073
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is determine whether the combination therapy with LEE011 and chemoembolization in patients with locally advanced Hepatocellular Carcinoma not amenable to curative therapies will provide greater efficacy than chemoembolization alone with a tolerable safety profile.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  CT Chest scans must be performed at baseline. CT-Chest/abdomen/pelvis must be performed every 8 weeks during the treatment phase (12 months). Once the patient has been discontinued from the study and enters the efficacy phase, radiological assessment (CT or MRI) will continue every 8 weeks until progression or for the first 12 months, whichever comes first. After a year, radiological (CT or MRI) assessments will be performed every 12 weeks for up to 1 year.

  Every 8 weeks for up to 3 years.

Secondary Outcomes (4)

• Overall Survival

  Every 12 weeks for up to 3 years.

• Number of Participants With Adverse Events

  Each visit for up to 3 years

• Tolerability, as Measured by Number of Adverse Events

  At each patient visit while on LEE001 for up to 3 years

• Objective Response Rate (ORR) Based on mRECIST and RECIST 1.1

  Every 8 weeks for 3 years

Study Arms (1)

LEE001 with Chemoembolization

EXPERIMENTAL

A total of 40 patients will be enrolled and undergo chemoembolization. Patients will receive LEE011 (600 mg PO once daily, 3 weeks on/1 week off) on Day 1 with chemoembolization. Patients can receive a total of 4 chemoembolization treatments within 6 month following first treatment as needed to treat initial HCC lesion.

Drug: LEE011; Procedure: Chemoembolization

Interventions

LEE011 DRUG

600 mg PO once daily will be given orally on days 1-21 of a 28 day cycle (3 weeks on / 1 week off) :until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment due to any other reason

LEE001 with Chemoembolization

Chemoembolization PROCEDURE

Patients will be treated with chemoembolization once every 4 weeks with up to 4 total chemoembolizations within the first 6 months from the initial chemoembolization.

LEE001 with Chemoembolization

Eligibility Criteria

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

You may qualify if:

• Patient must have a histologically confirmed diagnosis of RB positive hepatocellular carcinoma
• Patients must have HCC limited to the liver. There must be no clinical or radiographic evidence of extrahepatic HCC. Portal lymphadenopathy is permitted as lymphadenopathy is commonly associated with cirrhosis unrelated to malignancy;
• Absence of occlusive main portal vein thrombus, branch venous thrombus is allowed;
• Patients with locally advanced HCC not eligible for curative therapies;
• Age ≥ 18 years;
• Child-Pugh Score A or B7;
• ECOG (Eastern Cooperative Oncology Group) Performance score of 0-2;
• Life expectancy greater than 6 months;
• Following baseline laboratory values:
• Total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤1.5 x ULN in patients with well-documented Gilbert's Syndrome;
• INR (international normalized ratio) ≤ 1.7;
• Hgb ≥ 9.0 g/dl;
• Alkaline Phosphatase, AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase) \<7 times ULN;
• Platelet count ≥ 75,000/mm3;
• Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min;

You may not qualify if:

• Patient who received any CDK4/6 inhibitor (cyclin-dependent kinase 4);
• Patient who has received previous systemic therapy;
• Patients with central nervous system (CNS) involvement, unless they meet ALL of the following criteria:
• At least 4 weeks from prior therapy completion (including ration and/or surgery) to starting the study treatment;
• Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases;
• Clinically significant, uncontrolled heart disease and/or recent events including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening;
• History of documented congestive heart failure (New York Heart Association functional classification III-IV);
• Documented cardiomyopathy;
• Patient has a left ventricular ejection fraction \<50% as determined by MUGA (Multi Gated Acquisition scan) or ECHO at screening;
• History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrythmias, or conduction abnormality within 12 months of screening;
• Bradycardia (heart rate \<50 at rest), by ECG or pulse, at screening;
• Congenital long QT syndrome or family history of long QT syndrome;
• Systolic Blood Pressure (SBP) \>160 or \<90 mm Hg;
• On screening inability to determine the QTcF (Fridericia Correction Formula) interval on the ECG (i.e.: Unreadable or Not Interpretable) or QTcF \> 450 msec (using Fridericia's correction). All as determined by screening ECG (mean of triplicate ECGs);

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

ribociclib; Chemoembolization, Therapeutic

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Embolization, Therapeutic; Hemostatic Techniques; Therapeutics; Therapeutic Occlusion

Limitations and Caveats

Data were not collected for some outcome due to early study termination.

Results Point of Contact

• Title: Dr. Muhammad Beg
• Organization: UT Southwestern Medical Center

Muhammad.Beg@UTSouthwestern.edu

2146484180

Study Officials

• Muhammad Beg, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 14, 2015
• Study Start: April 1, 2016
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: February 1, 2021
• Results First Posted: February 1, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)