A Randomized Controlled Phase 2 Trial of ARQ 197 inPatients with Unresectable Hepatocellular Carcinoma(HCC) Who Have Failed One Prior Systemic Therapy

• Conditions: nresectable hepatocellular carcinoma (HCC); MedDRA version: 14.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-007155-27-DE
• Lead Sponsor: ArQule, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-08-07
• Last Update Posted: 10 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

Each prospective subject must meet ALL of the following inclusion
criteria in order to be eligible for this study:
1. Written informed consent granted prior to initiation of any study
specific screening procedures
2. 18 year of age or older
3. Histologically or cytologically confirmed HCC
4. Archival, fresh core needle biopsy or fine needle aspiration (FNA)
tumor samples
5. 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.
6. 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
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS)
=1 (Appendix 2)
8. 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.
9. 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 levels has increased by more than 30% since the last
AFP level taken one to four months prior to randomization).
10. Adequate bone marrow, liver, and renal functions at Pre-Study Visit,
defined as:
- Platelet count = 60 × 109/L
- Hemoglobin = 9.0 g/dL
- Absolute neutrophil count (ANC) =1.5 × 109/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
11. Women of childbearing potential must have a negative pregnancy
test performed within ten days prior to the start of study drug.
12. 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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

Exclusion Criteria

Potential subjects who meet ANY of the following exclusion criteria are
not eligible for enrollment into this study:
1. More than 1 prior systemic regimen.
2. Child-Pugh Class B-C cirrhotic status (See Appendix 4 for Child-Pugh
Classification)
3. 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.
4. 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 NCI 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).
5. Active clinically serious infections defined as = Grade 3 according to
NCI CTCAE, version 4.0.
6. 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
7. Any condition that is unstable or which could jeopardize the safety of
the patient and his/her protocol compliance
8. Known human immunodeficiency virus (HIV) infection
9. Pregnancy or breast-feeding.
10. History of liver transplant
11. Inability to swallow oral medications
12. Clinically significant gastrointestinal bleeding occurring =4 weeks
prior to randomization.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified