AZD6244 and Sorafenib in Advanced Hepatocellular Carcinoma

N

National Cancer Centre, Singapore

Status and phase

Terminated
Phase 2
Phase 1

Conditions

Hepatocellular Carcinoma

Treatments

Drug: AZD6244 and sorafenib

Study type

Interventional

Funder types

Other

Identifiers

NCT01029418
09-20-HEP

Details and patient eligibility

About

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

Full 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

Enrollment

30 patients

Sex

All

Ages

21+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

30 participants in 1 patient group

AZD6244 and sorafenib
Experimental group
Description:
AZD6244+ sorafenib
Treatment:
Drug: AZD6244 and sorafenib

Trial contacts and locations

2

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Data sourced from clinicaltrials.gov

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