Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)

July 11, 2012 updated by: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

A Phase 1b Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)

Multi-center, single-arm Phase 1b study designed to evaluate safety and tolerability of ARQ 197 in cirrhotic patients with HCC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study designed to evaluate safety and tolerability of ARQ 197 in cirrhotic patients with HCC who have received ≤2 prior systemic regimens for HCC, and whose liver disease severity is categorized as Class A and B per Child-Pugh Classification.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bologna, Italy, 15-40138
      • Milano, Italy, 20089
  • Spain
      • Barcelona, Spain, 08036
  • United States
    • Texas
      • Dallas, Texas, United States, 75246
      • Houston, Texas, United States, 77024

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice
  • 18 year of age or older
  • Histologically or cytologically confirmed HCC (not required if: a hepatic lesion is >2cm in diameter , is suggestive of HCC at radiology and α-fetoprotein (AFP) is > 200 mg/mL)
  • Barcelona Clinic Liver Cancer (BCLC) staging Category27 A, B or C that can not benefit from treatments of established efficacy and/or higher priority
  • Cirrhotic status of Child-Pugh Class A and B without ascites or with slight ascites that can be recognized only by imaging techniques and/or managed easily with diuretics (e.g. 100 mg spironolactone per day and/or furosemide 40 mg/day)
  • Cirrhotic status confirmed by one of the following methods/evidence:
  • Biopsy
  • Endoscopy showing gastrointestinal tract varices
  • Evidence of portal hypertension on imaging studies such as dilated portal vein, collateral circulation
  • ECOG PS ≤1
  • Not more than two prior systemic regimens for HCC and the last treatment must have been completed ≥4 weeks prior to first dose of ARQ 197
  • Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed ≥4 weeks prior to first dose of ARQ 197
  • Measurable disease as defined by revised Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Tumor lesions selected as target lesion(s) at baseline should not have been previously treated with local therapy (naïve tumor lesion)
  • Adequate bone marrow, liver, and renal functions, defined as:
  • Platelet count ≥ 60 × 10^9/L
  • Hemoglobin ≥ 8.5 g/dL
  • Absolute neutrophil count (ANC) ≥1.5 × 10^9/L
  • Total bilirubin ≤ 3 mg/dL
  • Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 5 × upper limit of normal (ULN)
  • Serum creatinine ≤1.5 × ULN
  • International normalized ratio (INR) ≤ 2.3 or PT ≤ 6.0 seconds above control. Patients who are therapeutically anticoagulated with an agent such as coumadin or heparin are allowed to participate provided that no prior evidence of underlying abnormality exists in these parameters
  • Albumin ≥ 2.8 g/dL
  • Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug
  • Male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received

Exclusion Criteria:

  • Previous or concurrent cancer that is distinct from HCC in primary site or histology, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated >3 years prior to enrollment is permitted
  • History of cardiac disease: congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia, or uncontrolled hypertension; myocardial infarction occurred within 6 months prior to study entry (myocardial infarction occurred > 6 months prior to study entry is permitted)
  • Active clinically serious infections defined as ≥ Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
  • Substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results
  • Any condition that is unstable or which could jeopardize the safety of the patient and his/her protocol compliance
  • Known HIV (human immunodeficiency virus) infection
  • Pregnancy or breast-feeding
  • History of liver transplant
  • Inability to swallow oral medications
  • Clinically significant gastrointestinal bleeding occurring ≤4 weeks prior to first dose of ARQ 197

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ARQ 197
Drug: ARQ 197
360 mg administered twice daily until disease progression, unacceptable toxicity, or other discontinuation criterion is met

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To evaluate the safety of ARQ 197 when administered in cirrhotic patients diagnosed with HCC

Secondary Outcome Measures

Outcome Measure
To evaluate time to disease progression (TTP), objective response rate (ORR), and disease control rate (DCR) in patients with HCC
To evaluate dynamic changes of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and soluble c-Met in patients' peripheral blood that are associated with ARQ 197 treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

December 4, 2008

First Submitted That Met QC Criteria

December 4, 2008

First Posted (Estimate)

December 5, 2008

Study Record Updates

Last Update Posted (Estimate)

July 12, 2012

Last Update Submitted That Met QC Criteria

July 11, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ARQ 197-114

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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