Trial of ARQ 197 in Patients With Unresectable Hepatocellular Carcinoma (HCC) Who Have Failed One Prior Systemic Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ArQule
ClinicalTrials.gov Identifier:
NCT00988741
First received: September 30, 2009
Last updated: February 22, 2013
Last verified: February 2013
  Purpose

This is a global randomized, placebo-controlled, double-blinded Phase 2 study designed to compare treatment of ARQ 197 versus placebo in patients with unresectable HCC who had radiographic disease progression after systemic first line therapy or were unable to tolerate the therapy.


Condition Intervention Phase
Unresectable Hepatocellular Carcinoma
Drug: ARQ 197
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Phase 2 Trial of ARQ 197 in Patients With Unresectable Hepatocellular Carcinoma (HCC) Who Have Failed One Prior Systemic Therapy

Resource links provided by NLM:


Further study details as provided by ArQule:

Primary Outcome Measures:
  • Evaluate time to progression among all patients treated with ARQ 197 compared to placebo [ Time Frame: Patients will be evaluated every 6 weeks until unacceptable toxicity, disease progression or another discontinuation criterion is met ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate progression-free survival, overall survival, objective response rate and disease control rate among all patients treated with ARQ 197 compared to placebo. [ Time Frame: Patients will be evaluated for these endpoints every 6 weeks ] [ Designated as safety issue: No ]
  • Evaluate objective response rate in crossover population following radiographic disease progression on placebo. [ Time Frame: Patients will be evaluated for these endpoints every 6 weeks ] [ Designated as safety issue: No ]
  • Further characterize the safety of ARQ 197 in patients with unresectable HCC [ Time Frame: While on therapy, patients will be evaluated for safety every 4 weeks ] [ Designated as safety issue: No ]
  • Further evaluate pharmacokinetics of ARQ 197. [ Time Frame: Patients will be evaluated monthly for the first 3 months ] [ Designated as safety issue: No ]

Enrollment: 107
Study Start Date: September 2009
Study Completion Date: March 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ARQ 197 Drug: ARQ 197
The investigational drug ARQ 197 is supplied as capsules. A dose of 360 mg (3 capsules of 120 mg each) of ARQ 197 will be administered by mouth BID, once in the morning and once in the evening with meals, for a total daily dose of 720 mg. Under Amendment 2, a dose of 240 mg (2 capsules of 120 mg each) of ARQ 197/placebo will be administered by mouth BID, once in the morning and once in the evening with meals, for a total daily dose of 480 mg. A treatment cycle is defined as 4 weeks for both treatment arms. Cycles will be repeated every 4 weeks (28 days) based on toxicity and response.
Other Name: Tivantinib
Placebo Comparator: placebo Drug: Placebo
The placebo is provided in a capsule form.

Detailed Description:

Patients will be randomly assigned in a 2:1 ratio to receive ARQ 197 or placebo. The treatment assignment will be stratified based on Eastern Cooperative Oncology Group (ECOG) performance status (PS), and vascular invasion status. The treatment with ARQ 197 or placebo will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion listed in this protocol is met.

After radiographic disease progression is documented, treatment assignment will be unblinded. Patients who were assigned to placebo arm and had documented radiographic disease progression will have the option to receive ARQ 197 and will be evaluated for objective response rate and disease control rate continuously.

The study will continue until 78 total time to progression events are reached. At the end of study, all remaining patients still on treatment will have the option to be rolled over to another study to continue their treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent granted prior to initiation of any study-specific screening procedures
  • 18 year of age or older
  • Histologically or cytologically confirmed HCC
  • Archival, fresh core needle biopsy or fine needle aspiration (FNA) tumor samples
  • Received at least one cycle of prior systemic therapy (at least 3 weeks for continuously administered drugs) and experienced radiographic disease progression or was unable to tolerate therapy. If intolerance was manifested by a Grade 3 or 4 event of such nature that re-challenge is not acceptable, less than 3 weeks of continuous administration will be allowed
  • Discontinued prior treatment for at least 4 weeks, or at least 2 weeks (14 days) if drug was administered continuously and orally (e.g. sorafenib or sunitinib), prior to the study randomization
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1
  • 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 randomization
  • Measurable disease as defined by a modified version of the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (see section 9). Tumor lesions previously treated with local therapy should demonstrate clear dimensional increase by radiographic assessment in order to be selected as target lesion(s) at baseline. (Radiological assessment needs to be redone within 7 days prior to randomization if the pre-study AFP level has increased by more than 30% since the last AFP level taken one to four months prior to randomization)
  • Adequate bone marrow, liver, and renal functions at Pre-Study Visit, defined as:

    • Platelet count ≥ 60 × 10^9/L
    • Hemoglobin ≥ 9.0 g/dL
    • Absolute neutrophil count (ANC) ≥1.5 × 10^9/L
    • Total bilirubin ≤ 2 mg/dL
    • Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 5 × upper limit of normal (ULN)
    • Serum creatinine ≤1.5 × ULN
    • International normalized ratio (INR) 0.8 to 1.4 or ≤3 for patients receiving anticoagulant such as coumadin or heparin. Patients who are therapeutically anticoagulated 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 ten 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:

  • More than 1 prior systemic regimen
  • Child-Pugh B-C cirrhotic status
  • 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 congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within 6 months prior to study entry; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as ≥Grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring >6 months prior to study entry is permitted)
  • Active clinically serious infections defined as ≥ Grade 3 according to NCI CTCAE, version 4.0.
  • 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 human immunodeficiency virus (HIV) infection
  • Pregnancy or breast-feeding
  • History of liver transplant
  • Inability to swallow oral medications
  • Clinically significant gastrointestinal bleeding occurring ≤4 weeks prior to randomization
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00988741

Locations
United States, California
Los Angeles, California, United States, 90048
United States, Florida
Tampa, Florida, United States, 33612
United States, Texas
Galveston, Texas, United States, 77555
Belgium
Brussels, Belgium, 1200
Brussels, Belgium, 1070
Gent, Belgium, 9000
Canada
Toronto, Canada, M5G 2N2
Vancouver, Canada, V5Z 1M9
Germany
Essen, Germany, 45123
Frankfurt am Main, Germany, D-60594
Hamburg, Germany, 20099
Munchen, Germany, 81657
Munchen, Germany, 81337
Italy
Avellino, Italy, 83100
Benevento, Italy, 82100
Bologna, Italy, 40138
Padova, Italy, 35128
Parma, Italy, 43126
Pavia, Italy, 27100
Pisa, Italy, 56100
Reggio Emilia, Italy, 42100
Roma, Italy, 00168
Rozzano Milano, Italy, 20089
Sponsors and Collaborators
ArQule
  More Information

No publications provided by ArQule

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: ArQule
ClinicalTrials.gov Identifier: NCT00988741     History of Changes
Other Study ID Numbers: ARQ 197-215
Study First Received: September 30, 2009
Last Updated: February 22, 2013
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Belgium: Ministry of Social Affairs, Public Health and the Environment
Italy: Ministry of Health
Canada: Health Canada

Keywords provided by ArQule:
Unresectable
Hepatocellular
Carcinoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on April 16, 2014