AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Choo Su Pin, National Cancer Centre, Singapore
ClinicalTrials.gov Identifier:
NCT01029418
First received: December 9, 2009
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

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 Intervention Phase
Unresectable Hepatocellular Carcinoma
Liver Cancer
Drug: AZD6244 and sorafenib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of AZD6244 in Combination With Sorafenib in Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Centre, Singapore:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 166
Study Start Date: November 2009
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: study drugs
AZD6244+ sorafenib
Drug: AZD6244 and sorafenib
dose escalation of AZD6244; sorafenib 400mg bd
Other Names:
  • AZD6244,
  • MEK inhibitor,
  • sorafenib,
  • Raf kinase inhibitor
  • nexavar

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

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01029418

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

Publications:
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
Study First Received: December 9, 2009
Last Updated: November 7, 2012
Health Authority: Singapore: Health Sciences Authority

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

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Carcinoma
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014