CirrhosisPhase 1NCT00802555
Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)
A Phase 1 study testing ARQ 197 in people with Cirrhosis and Hepatocellular Carcinoma, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 5 sites in 3 countries.
Trial summary
Multi-center, single-arm Phase 1b study designed to evaluate safety and tolerability of ARQ 197 in cirrhotic patients with HCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Hepatocellular Carcinoma
- What is being tested?
- ARQ 197
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Jan 2009to Dec 2011
- Phase
- Phase 1
- 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, 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:
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States2 sites
Study site
Dallas, Texas, 75246
Study site
Houston, Texas, 77024
About this study
Official title: A Phase 1b Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)
Multi-center, single-arm Phase 1b study designed to evaluate safety and tolerability of ARQ 197 in cirrhotic patients with HCC.
Read the 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.
- Conditions
- Cirrhosis, Hepatocellular Carcinoma
- Being tested
- ARQ 197
- Keywords
- HCC, Cirrhotic Patients with Hepatocellular Carcinoma
- Medical subject headings
- Fibrosis, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARQ 197Drug
360 mg administered twice daily until disease progression, unacceptable toxicity, or other discontinuation criterion is met
| Study group | Role | What they receive |
|---|---|---|
| ARQ 197 | Experimental | Not described Receives: Drug: ARQ 197 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2008 (estimated)
- Study startJan 2009
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00802555
- Sponsor's protocol ID
- ARQ 197-114
- Status last verified
- Jul 2012
- First submitted
- 4 Dec 2008
- Last updated
- 12 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Safety Study of ARQ 197 in Cirrhotic Patients With Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT00802555
- Acronym / sponsor ID
- ARQ 197-114
- Conditions
- Cirrhosis, Hepatocellular Carcinoma
- Keywords
- HCC, Cirrhotic Patients with Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)Industry (pharma, biotech, devices)
- Study start
- Jan 2009
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 5 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ARQ 197 | Experimental | Drug: ARQ 197 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARQ 197360 mg administered twice daily until disease progression, unacceptable toxicity, or other discontinuation criterion is met | Drug | ARQ 197 |
Primary outcome
To evaluate the safety of ARQ 197 when administered in cirrhotic patients diagnosed with HCC
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ARQ 197 in people with Cirrhosis and Hepatocellular Carcinoma, run by ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) at 5 sites in 3 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 24 inclusion and 10 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 12 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Italy, Spain. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
To evaluate the safety of ARQ 197 when administered in cirrhotic patients diagnosed with HCC. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jul 2012.