AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma
Information source: National Cancer Centre, Singapore
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatocellular Carcinoma
Intervention: AZD6244 and sorafenib (Drug)
Phase: Phase 1/Phase 2
Status: Terminated
Sponsored by: National Cancer Centre, Singapore Official(s) and/or principal investigator(s): Su Pin Choo, Principal Investigator, Affiliation: National Cancer Centre, Singapore
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
Clinical Details
Official title: A Phase 1/2 Study of AZD6244 in Combination With Sorafenib in Advanced Hepatocellular Carcinoma
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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.
Secondary outcome: To investigate if the combination sorafenib and AZD6244 increases Time To Progression (TTP) over sorafenib alone in patients with advanced hepatocellular carcinoma patients.
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
Eligibility
Minimum age: 21 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
National Cancer Centre Singapore, Singapore 169610, Singapore
National University Hospital Singapore, Singapore 119074, Singapore
Additional Information
Related publications: 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.
Starting date: November 2009
Last updated: April 14, 2015
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