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AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma

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ClinicalTrials.gov Identifier: NCT01029418
Recruitment Status : Terminated (The phase II portion was not conducted due to funding issue.)
First Posted : December 10, 2009
Last Update Posted : April 16, 2015
Sponsor:
Information provided by (Responsible Party):
Choo Su Pin, National Cancer Centre, Singapore

Study Description
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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

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: AZD6244 and sorafenib Phase 1 Phase 2

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of AZD6244 in Combination With Sorafenib in Advanced Hepatocellular Carcinoma
Study Start Date : November 2009
Actual Primary Completion Date : February 2014
Actual Study Completion Date : January 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: AZD6244 and sorafenib
AZD6244+ sorafenib
 Drug: AZD6244 and sorafenib
dose escalation of AZD6244; sorafenib 400mg bd
Other Names:
  • AZD6244,
  • MEK inhibitor,
  • sorafenib,
  • Raf kinase inhibitor
  • nexavar


Outcome Measures
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Primary Outcome Measures :
  1. 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. [ Time Frame: 12-15months ]

Secondary Outcome Measures :
  1. To investigate if the combination sorafenib and AZD6244 increases Time To Progression (TTP) over sorafenib alone in patients with advanced hepatocellular carcinoma patients. [ Time Frame: 2-3 years ]

Eligibility Criteria
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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01029418


Locations
Singapore
National University Hospital Singapore
Singapore, Singapore, 119074
National Cancer Centre Singapore
Singapore, Singapore, 169610
Sponsors and Collaborators
National Cancer Centre, Singapore
Investigators
Principal Investigator: Su Pin Choo National Cancer Centre, Singapore
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Choo Su Pin, Senior Consultant, National Cancer Centre, Singapore
ClinicalTrials.gov Identifier: NCT01029418     History of Changes
Other Study ID Numbers: 09-20-HEP
First Posted: December 10, 2009    Key Record Dates
Last Update Posted: April 16, 2015
Last Verified: April 2015

Keywords provided by Choo Su Pin, National Cancer Centre, Singapore:
HCC
hepatocellular carcinoma
liver cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
 Sorafenib
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs