Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)
Primary Purpose
Cirrhosis, Hepatocellular Carcinoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ARQ 197
Sponsored by

About this trial
This is an interventional treatment trial for Cirrhosis focused on measuring HCC, Cirrhotic Patients with Hepatocellular Carcinoma
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ARQ 197
Arm Description
Outcomes
Primary Outcome Measures
To evaluate the safety of ARQ 197 when administered in cirrhotic patients diagnosed with HCC
Secondary Outcome Measures
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
Full Information
NCT ID
NCT00802555
First Posted
December 4, 2008
Last Updated
July 11, 2012
Sponsor
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
1. Study Identification
Unique Protocol Identification Number
NCT00802555
Brief Title
Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)
Official Title
A Phase 1b Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2012
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Multi-center, single-arm Phase 1b study designed to evaluate safety and tolerability of ARQ 197 in cirrhotic patients with HCC.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis, Hepatocellular Carcinoma
Keywords
HCC, Cirrhotic Patients with Hepatocellular Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ARQ 197
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ARQ 197
Intervention Description
360 mg administered twice daily until disease progression, unacceptable toxicity, or other discontinuation criterion is met
Primary Outcome Measure Information:
Title
To evaluate the safety of ARQ 197 when administered in cirrhotic patients diagnosed with HCC
Secondary Outcome Measure Information:
Title
To evaluate time to disease progression (TTP), objective response rate (ORR), and disease control rate (DCR) in patients with HCC
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
City
Bologna
ZIP/Postal Code
15-40138
Country
Italy
City
Milano
ZIP/Postal Code
20089
Country
Italy
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
12. IPD Sharing Statement
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Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)
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