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Unresectable Hepatocellular CarcinomaPhase 2NCT00988741

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

A Phase 2 study testing ARQ 197 in people with Unresectable Hepatocellular Carcinoma, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 23 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Unresectable Hepatocellular Carcinoma
What is being tested?
ARQ 197
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
107 participants
Where
23 sitesin 5 countries
Study dates
Sep 2009to Mar 2012
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

23 sites in 5 countries.

23 sites in 5 countries

Italy10 sites

  • Study site

    Avellino, 83100

  • Study site

    Benevento, 82100

  • Study site

    Bologna, 40138

  • Study site

    Padova, 35128

  • Study site

    Parma, 43126

  • Study site

    Pavia, 27100

  • Study site

    Pisa, 56100

  • Study site

    Reggio Emilia, 42100

  • Study site

    Roma, 00168

  • Study site

    Rozzano Milano, 20089

Other trials in Italy

Germany5 sites

  • Study site

    Essen, 45123

  • Study site

    Frankfurt am Main, D-60594

  • Study site

    Hamburg, 20099

  • Study site

    München, 81337

  • Study site

    München, 81657

Other trials in Germany

United States3 sites

  • Study site

    Galveston, Texas, 77555

  • Study site

    Los Angeles, California, 90048

  • Study site

    Tampa, Florida, 33612

Other trials in United States

Belgium3 sites

  • Study site

    Brussels, 1070

  • Study site

    Brussels, 1200

  • Study site

    Ghent, 9000

Other trials in Belgium

Canada2 sites

  • Study site

    Toronto, M5G 2N2

  • Study site

    Vancouver, V5Z 1M9

Other trials in Canada

About this study

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

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.

Read the 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.

Being tested
ARQ 197, Placebo
Keywords
Unresectable, Hepatocellular, Carcinoma
Medical subject headings
Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARQ 197Drug

    Also called Tivantinib

    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.

  • PlaceboDrug

    The placebo is provided in a capsule form.

Study groups in NCT00988741
Study groupRoleWhat they receive
ARQ 197ExperimentalNot described
Receives: Drug: ARQ 197
placeboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

Secondary outcomes (4)

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

    Measured: Patients will be evaluated for these endpoints every 6 weeks

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

    Measured: Patients will be evaluated for these endpoints every 6 weeks

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

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

  4. Further evaluate pharmacokinetics of ARQ 197.

    Measured: Patients will be evaluated monthly for the first 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Oct 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionOct 2011
  4. Study completionMar 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
107 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00988741
Sponsor's protocol ID
ARQ 197-215
Status last verified
Feb 2013
First submitted
30 Sep 2009
Last updated
28 Feb 2013
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 23182627

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ARQ 197 in people with Unresectable Hepatocellular Carcinoma, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 23 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Italy, Germany, United States, Belgium, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00988741, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2013.

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