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

NCT00988741 | Completed Phase 2

• 1 other identifier: ARQ 197-215
• Study Type: interventional
• Target: 107
• Locations: 5 countries
• Sites: 23

Brief Summary

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.

Conditions

Unresectable Hepatocellular Carcinoma

Keywords

Unresectable; Hepatocellular; Carcinoma

Outcome Measures

Primary Outcomes (1)

• Evaluate time to progression among all patients treated with ARQ 197 compared to placebo

  Patients will be evaluated every 6 weeks until unacceptable toxicity, disease progression or another discontinuation criterion is met

Secondary Outcomes (4)

• Evaluate progression-free survival, overall survival, objective response rate and disease control rate among all patients treated with ARQ 197 compared to placebo.

  Patients will be evaluated for these endpoints every 6 weeks

• Evaluate objective response rate in crossover population following radiographic disease progression on placebo.

  Patients will be evaluated for these endpoints every 6 weeks

• Further characterize the safety of ARQ 197 in patients with unresectable HCC

  While on therapy, patients will be evaluated for safety every 4 weeks

• Further evaluate pharmacokinetics of ARQ 197.

  Patients will be evaluated monthly for the first 3 months

Study Arms (2)

ARQ 197

EXPERIMENTAL

Drug: ARQ 197

placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ARQ 197 DRUG

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.

Also known as: Tivantinib

ARQ 197

Placebo DRUG

The placebo is provided in a capsule form.

placebo

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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (23)

Unknown Facility

Los Angeles, California, 90048, United States

Location

Unknown Facility

Tampa, Florida, 33612, United States

Location

Unknown Facility

Galveston, Texas, 77555, United States

Location

Unknown Facility

Brussels, 1070, Belgium

Location

Unknown Facility

Brussels, 1200, Belgium

Location

Unknown Facility

Ghent, 9000, Belgium

Location

Unknown Facility

Toronto, M5G 2N2, Canada

Location

Unknown Facility

Vancouver, V5Z 1M9, Canada

Location

Unknown Facility

Essen, 45123, Germany

Location

Unknown Facility

Frankfurt am Main, D-60594, Germany

Location

Unknown Facility

Hamburg, 20099, Germany

Location

Unknown Facility

München, 81337, Germany

Location

Unknown Facility

München, 81657, Germany

Location

Unknown Facility

Avellino, 83100, Italy

Location

Unknown Facility

Benevento, 82100, Italy

Location

Unknown Facility

Bologna, 40138, Italy

Location

Unknown Facility

Padua, 35128, Italy

Location

Unknown Facility

Parma, 43126, Italy

Location

Unknown Facility

Pavia, 27100, Italy

Location

Unknown Facility

Pisa, 56100, Italy

Location

Unknown Facility

Reggio Emilia, 42100, Italy

Location

Unknown Facility

Roma, 00168, Italy

Location

Unknown Facility

Rozzano Milano, 20089, Italy

Location

Related Publications (1)

• Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, Van Vlierberghe H, Trojan J, Kolligs FT, Weiss A, Miles S, Gasbarrini A, Lencioni M, Cicalese L, Sherman M, Gridelli C, Buggisch P, Gerken G, Schmid RM, Boni C, Personeni N, Hassoun Z, Abbadessa G, Schwartz B, Von Roemeling R, Lamar ME, Chen Y, Porta C. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol. 2013 Jan;14(1):55-63. doi: 10.1016/S1470-2045(12)70490-4. Epub 2012 Nov 20.

  PMID: 23182627 DERIVED

MeSH Terms

Conditions

Carcinoma

Interventions

ARQ 197

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

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: September 30, 2009
• First Posted: October 2, 2009
• Study Start: September 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: March 1, 2012
• Last Updated: February 28, 2013

Record last verified: 2013-02

Locations

IT (10); US (3); BE (3); CA (2); DE (5)