AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma

National Cancer Centre, Singapore

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Hepatocellular Carcinoma

Treatments

Drug: AZD6244 and sorafenib

Study type

Interventional

Funder types

Other

Identifiers

NCT01029418

09-20-HEP

Details and patient eligibility

About

This will be a phase I/II clinical trial testing the combination of sorafenib and AZD6244 in advanced hepatocellular carcinoma with Childs A liver cirrhosis. The aim of the phase I portion is to determine appropriate dose of this drug combination. The phase 2 study will look at effectiveness and safety of this drug combination

Full description

Patients with unresectable BCLC Stage B/C hepatocellular carcinoma that is biopsy-proven ( histology or cytology from prior tumor biopsy specimen is acceptable Patients without prior systemic treatment ( chemotherapy or molecular targeted therapy) except prior adjuvant therapy, if given more than 6 months ago Child-Pugh class A only ECOG performance status 0 or 1

Enrollment

30 patients

Sex

All

Ages

21+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with unresectable BCLC Stage B/C hepatocellular carcinoma that is biopsy-proven ( histology or cytology from prior tumor biopsy specimen is acceptable)
Patients without prior systemic treatment ( chemotherapy or molecular targeted therapy) except prior adjuvant therapy, if given more than 6 months ago
Patients who had prior local therapy ( TACE; PEI; RFA) more than 4 weeks prior to study entry
No radiotherapy within 4 weeks before entry
Child-Pugh class A only ( Appendix A)
Age 21 years and older
ECOG performance status 0 or 1 ( Appendix A)
Life expectancy > 3 months.
Patients must have normal organ and marrow function as defined below:

Absolute neutrophil count > 1.5 x 109/L;Platelets> 75 x 109/L; Haemoglobin > 9.0g/dl;Total bilirubin < 51umol/L ( 3 mg /dL); AST(SGOT)/ALT(SGPT) < 5 X institutional ULN; Creatinine 1.5 ULN; INR <1.7 or prothrombin time ( PT) <4 seconds above ULN; Left ventricular ejection fraction (LVEF) >50%

Measurable disease according to RECIST. A lesion which has previously been locally treated (including TACE or RFA) is eligible as long as there is evidence of disease progression
Suitable for oral administration of drug
Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

Prior systemic therapy including sorafenib or a MEK inhibitor or sunitinib or other investigational drugs
Any prior local therapy ( surgery, radiation therapy, hepatic arterial embolization, or cryoablation) within 4 weeks of study entry.
Prior liver transplant
NCI CTCAE grade > 3 hemorrhage within 4 weeks of starting study treatment, or documented variceal hemorrhage of any grade within 12 months of study entry (as documented on endoscopy)
Presence of esophageal varices (> Grade 2) at risk of bleeding and/or serious or non-healing wound/ulcer ( as documented by endoscopy)
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study entry
Patients with underlying inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea
Any of the following within the 12 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, including transient ischemic attack, or pulmonary embolism.
History of cardiac disease:
active congestive heart failure
cardiac arrythmias of NCI CTCAE grade >2 or requiring pacemaker
uncontrolled hypertension
cardiomyopathy
atrial fibrillation rate >100bpm
Patients with factors that increase the risk of QT prolongation or arrhythmic events ( hypokalemia, family history of long QT interval syndrome) or QTc interval of > 450ms for males or > 470ms for females on screening