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

NCT00802555 | Completed Phase 1

• 1 other identifier: ARQ 197-114
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• Sites: 5

Brief Summary

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

Conditions

Cirrhosis; Hepatocellular Carcinoma

Keywords

HCC; Cirrhotic Patients with Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (2)

• 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

Study Arms (1)

ARQ 197

EXPERIMENTAL

Drug: ARQ 197

Interventions

ARQ 197 DRUG

360 mg administered twice daily until disease progression, unacceptable toxicity, or other discontinuation criterion is met

ARQ 197

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA): lead

Study Sites (5)

Unknown Facility

Dallas, Texas, 75246, United States

Location

Unknown Facility

Houston, Texas, 77024, United States

Location

Unknown Facility

Bologna, 15-40138, Italy

Location

Unknown Facility

Milan, 20089, Italy

Location

Unknown Facility

Barcelona, 08036, Spain

Location

MeSH Terms

Conditions

Fibrosis; Carcinoma, Hepatocellular

Interventions

ARQ 197

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2008
• First Posted: December 5, 2008
• Study Start: January 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: July 12, 2012

Record last verified: 2012-07

Locations

IT (2); US (2); ES (1)