AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma

NCT ID: NCT01029418

Last Updated: 2015-04-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2015-01-31

Brief Summary

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

Detailed 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

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AZD6244 and sorafenib

AZD6244+ sorafenib

Group Type: EXPERIMENTAL

AZD6244 and sorafenib

Intervention Type: DRUG

dose escalation of AZD6244; sorafenib 400mg bd

Interventions

AZD6244 and sorafenib

dose escalation of AZD6244; sorafenib 400mg bd

Intervention Type: DRUG

Other Intervention Names

AZD6244,; MEK inhibitor,; sorafenib,; Raf kinase inhibitor; nexavar

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Centre, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Choo Su Pin

Senior Consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Su Pin Choo

Role: PRINCIPAL_INVESTIGATOR

National Cancer Centre, Singapore

Locations

National University Hospital Singapore

Singapore, , Singapore

National Cancer Centre Singapore

Singapore, , Singapore

Countries

Singapore

References

Huynh H, Ngo VC, Koong HN, Poon D, Choo SP, Toh HC, Thng CH, Chow P, Ong HS, Chung A, Goh BC, Smith PD, Soo KC. AZD6244 enhances the anti-tumor activity of sorafenib in ectopic and orthotopic models of human hepatocellular carcinoma (HCC). J Hepatol. 2010 Jan;52(1):79-87. doi: 10.1016/j.jhep.2009.10.008. Epub 2009 Oct 28.

Reference Type: BACKGROUND

PMID: 19910069 (View on PubMed)

Tai WM, Yong WP, Lim C, Low LS, Tham CK, Koh TS, Ng QS, Wang WW, Wang LZ, Hartano S, Thng CH, Huynh H, Lim KT, Toh HC, Goh BC, Choo SP. A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC). Ann Oncol. 2016 Dec;27(12):2210-2215. doi: 10.1093/annonc/mdw415. Epub 2016 Sep 28.

Reference Type: DERIVED

PMID: 27681866 (View on PubMed)

Other Identifiers

09-20-HEP

Identifier Type: -

Identifier Source: org_study_id