AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase 1/2 Study of AZD6244 in Combination With Sorafenib in Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01029418
• Other study ID #: 09-20-HEP
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: December 9, 2009
• Last updated: April 14, 2015
• Start date: November 2009
• Est. completion date: January 2015

Study information

• Verified date: April 2015
• Source: National Cancer Centre, Singapore
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Health Sciences Authority
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: January 2015
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• AZD6244 and sorafenib
dose escalation of AZD6244; sorafenib 400mg bd

Locations

Country	Name	City	State
Singapore	National Cancer Centre Singapore	Singapore
Singapore	National University Hospital Singapore	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Centre, Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination of AZD6244 and sorafenib in patients with advanced hepatocellular cancer.		12-15months	Yes
Secondary	To investigate if the combination sorafenib and AZD6244 increases Time To Progression (TTP) over sorafenib alone in patients with advanced hepatocellular carcinoma patients.		2-3 years	Yes