Study of Sorafenib With or Without VT-122 in Patients With Hepatocellular Carcinoma (HCC)

NCT01265576 | Unknown Phase 2 DMC

• 1 other identifier: VT1-CAX-200
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to determine if VT-122 provides a clinical benefit when added to Sorafenib in patients with advanced hepatocellular carcinoma (HCC).

Conditions

HCC

Outcome Measures

Primary Outcomes (1)

• failure free survival

  6 months

Secondary Outcomes (1)

• clinical benefit response

  6 months

Study Arms (2)

Sorafenib with placebo

PLACEBO COMPARATOR

Participants randomized to the Control Arm (sorafenib with placebo) receive sorafenib as the standard of care, and placebo for the same periods as participants randomized to the Treatment Arm (sorafenib plus VT-122). Participants randomized to the Control Arm will undergo the same visits and procedures as would the participants randomized to the Treatment Arm.

Drug: Sorafenib; Drug: Placebo

Sorafenib plus VT-122

EXPERIMENTAL

Drug: Sorafenib; Drug: VT-122 (propranolol plus etodolac)

Interventions

Sorafenib DRUG

Participants will be on sorafenib at least 30 days before randomization into either the Treatment or Control Arms. Sorafenib will be administered according to the package insert unless contraindicated based on physician expertise.

Sorafenib plus VT-122; Sorafenib with placebo

VT-122 (propranolol plus etodolac) DRUG

Participants randomized to the VT-122 regimen (sorafenib plus VT-122) will receive oral doses of propranolol and etodolac, which will be titrated over a period of 3 weeks until the participant reaches a maximum tolerated dose (MTD)\[no higher than 60 mg propranolol, twice daily (BID)/300 mg etodolac, BID\]. Once the individual MTD has been reached, participants will enter a Maintenance Treatment period, and will receive the VT-122 regimen (propranolol and etodolac, co administered orally) on a continuous BID dosing schedule for a maximum of twelve 4-week cycles.

Sorafenib plus VT-122

Placebo DRUG

Participants randomized to the Control Arm (sorafenib with placebo) will receive placebo for the same periods as participants randomized to the Treatment Arm. Participants in the Control Arm will undergo the same visits and mock dose escalation.

Sorafenib with placebo

Eligibility Criteria

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

You may qualify if:

• Participants will be required to meet all of the following criteria to be considered eligible for the study:
• Have a confirmed diagnosis of HCC. Biopsy is preferred but is not required.
• Male and female participants who are ≥18 years of age.
• In the opinion of the investigator, the participants have a life expectancy of at least 12 weeks.
• Able to take food or nutritional support orally.
• On sorafenib for at least 4 weeks prior to randomization. Dose adjustments are allowed prior to randomization.
• Have a Karnofsky Performance Score (KPS) equal to or greater than 50.
• Have a cirrhotic status of Child-Pugh Class A or B7.
• Have the following laboratory parameters:
• a. Platelet count ≥50 x 10E9/L.
• b. Total bilirubin ≤1.5 mg/dL (≤1.0 mg/dL for primary biliary cirrhosis). If total bilirubin \>1.5 mg/dL but \<3.0 mg/dL, a patient could be enrolled after consultation with the Medical Monitor. If total bilirubin is \>3.0 mg/dL, but the value has been constant for a period of greater than 3 months, a patient could be enrolled after consultation with the Medical Monitor.
• c. Serum creatinine ≤1.5 x upper limit of normal (ULN) or creatinine clearance \>60 mL/min calculated using Cockcroft-Gault.
• d. Serum albumin ≤3.5 g/dL and/or C-reactive protein (CRP) ≥3 mg/L
• Able to provide written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, for any reason without prejudice.

You may not qualify if:

• The patient has a history of another primary cancer, with the exception of: a) curatively resected non-melanomatous skin cancer; b) curatively treated cervical carcinoma in-situ; or c) other primary solid tumor with no known active disease present that in the opinion of the investigator will not affect patient outcome in the setting of current HCC diagnosis.
• Contraindication to sorafenib, propranolol, etodolac, or placebo.
• Patient currently on beta-blockers for the treatment of portal hypertension or arrhythmia. \[Patients on beta blockers for the treatment of hypertension are allowed if they change to a different drug class, e.g. some classes of angiotensin-converting enzyme (ACE) inhibitors, for controlling hypertension at least one week before randomization\].
• Body mass index (BMI) \<17.5 kg/m2.
• History or evidence of cardiac disease: congestive heart failure; New York Heart Association class 2 or greater; active coronary artery disease; unstable angina, cardiac arrhythmias requiring anti-arrhythmic therapy, atrioventricular block of second or third degree, or uncontrolled hypertension. Patients with recent (less than 6 months) myocardial infarction (MI) or coronary revascularization.
• Hypotension at the time of screening (i.e., systolic blood pressure \<90 mmHg, diastolic blood pressure \<60 mmHg).
• Resting heart rate \<60 bpm at time of screening.
• Participants with a recent diagnosis of bleeding varices that has not been resolved for a minimum period of 4 weeks.
• Any uncontrolled intercurrent illness that, in the opinion of the Investigator, may interfere with study evaluation.
• On chronotropic drugs (acetylcholine, digoxin, diltiazem, verapamil, atropine, dopamine, dobutamine, epinephrine, isoproterenol).
• Active clinically serious infections \[\>Grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0\].
• Known history of human immunodeficiency virus (HIV) infection.
• Known central nervous system tumors including metastatic brain disease.
• Clinically significant gastrointestinal (GI) bleeding within 30 days prior to Screening.
• Substance abuse, medical, psychological or social conditions that may, in the in the opinion of the investigator, interfere with the patient's participation in the study or evaluation of the study results.

Sponsors & Collaborators

• Vicus Therapeutics: lead

Study Sites (10)

Vicus Clinical Site

Berkeley, California, 94704, United States

Location

Vicus Clinical Site

Atlanta, Georgia, 30318, United States

Location

Vicus Clinical Site

New Brunswick, New Jersey, United States

Location

Vicus Clinical Site

Newark, New Jersey, 07103, United States

Location

Vicus Clinical Site

Paterson, New Jersey, 07503, United States

Location

Vicus Clinical Site

Buffalo, New York, 14263, United States

Location

Vicus Clinical Site

New York, New York, 10016, United States

Location

Vicus Clinical Site

Philadelphia, Pennsylvania, United States

Location

Vicus Clinical Site

Houston, Texas, 77024, United States

Location

Vicus Clinical Site

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

Sorafenib; Propranolol; Etodolac

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Indoleacetic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2010
• First Posted: December 23, 2010
• Study Start: December 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: April 1, 2016
• Last Updated: December 9, 2015

Record last verified: 2015-12

Locations

US (10)